Anodic a-acetoxylation

The anodic a-acetoxylation or a-methoxylation of ketones has been shown to be a powerful tool for the 1,2-transposition of the caibonyl group. The overall process is described by equation (24). ... 

Table 19 shows results from the a-acetoxylation of two 2-alkyl-indans under different conditions analogous homogeneous reactions are included for comparison. Table 19 demonstrates that, at most, a weak effect is noticeable in the case of 2-t-butylindan, in that anodic oxidation on platinum, a strongly adsorbing metal, gives a cis/trans ratio that is about 10 times that observed from a 2-t-butyl-1-indanyl cation generated by solvolysis. Ratios on the weaker adsorbing electrode materials, carbon and lead dioxide, fall in between. For a smaller substituent (R = methyl) no effect is observable. 

Anodic a-methoxylation of phenyl 2,2,2-trifluoroethyl sulfide was carried out using various solid-supported bases as shown in Equation 12.6. Polystyrene and silica -gel are suitable as the solid support for an organic base such as piperidine. It is noteworthy that anodic methoxylation was successfully carried out even after 10 recycles of the solid-supported base. The method has also been successfully applied to electrochemical acetoxylation in acetic add/acetonitrile. 

On the contrary, the anodic acetoxylation is markedly promoted by per-fluoroalkyl groups (Eq. 27) [46]. It is notable that the promotion effect of a CF3 group on the anodic methoxylation is more pronounced than that of a CN group although the CF3 group has a smaller electron-withdrawing effect than CN. 

BASF has developed a direct electrochemical process based on anodic acetoxylation for the production of aromatic aldehydes on industrial scale [40,146,147]. The reaction passes smoothly through the benzyl acetate stage. 

Anodic oxidation of 2-t-butylindan in acetic acid led predominantly to side-chain acetoxylation at a Pt or Pb02 anode. The cis/trans ratio of the two acetates is significantly higher in the anodic process than in the related homogeneous reactions, indicating that adsorption at least partially controls the anodic reaction [206, 207]. Menthyl 4-methoxyarylacetate (5) could be... 

Acetoxylation proceeds mostly via the radical cation of the olefin. Aliphatic alkenes, however, undergo allylic substitution and rearrangement predominantly rather than addition [224, 225]. Aryl-substituted alkenes react by addition to vic-disubstituted acetates, in which the dia-stereoselectivity of the product formation indicates a cyclic acetoxonium ion as intermediate [226, 227]. In acenaphthenes, the cis portion of the diacetoxy product is significantly larger in the anodic process than in the chemical ones indicating that some steric shielding through the electrode is involved [228]. 

The anodic oxidation of 4-methoxyphcnols in acetic acid effectively stabilises the phenoxonium ion, in an equlibrium with the acetoxylation product. Tbis allows an intermolecular [5 + 2] bx-cycloaddition processes with some alkenes [110], The cycloaddition process has been used very successfully in the synthesis of a number of natural products [III]. The rate of cycloaddition is sensitive to substituents on the alkene bond and in imfavourable cases other reactions of the phenoxonium ion predominate. 

Anodic aromatic nuclear substitution is performed to introduce a hydroxy function leading to phenolic compounds. In the first step, acetoxylation or trifluoroacetoxylation occurs usually at carbon electrodes using the acid as solvent [5] ... 

The anode acetoxylation of aromatic compounds in solutions of acetic acid carrying alkali or tetraalkylammonium acetates takes the same route. As shown (Eberson 1967 Eberson Jonsson 1981), the process starts with one-electron oxidation at the anode and then passes through the same stages as on oxidation with cobalt trifluoroacetate. The reaction takes place at potentials sufficient to oxidize the substrate but not sufficient to convert the acetate ion into the acetoxy radical. Interestingly, the acetoxyl group comes to the product not from acetic acid (a solvent) but from the acetate ion (a conducting electrolyte) Salts with the tosylate or perchlorate anions stop the acetoxylation in the solution of acetic acid. 

Anodic acetoxylation is an illustrative example of these principles. Anodic oxidation of sodium acetate in acetic acid at a platinum anode under constant current conditions yields ethane in almost quantitative yield. The mechanism was supposed to be discharge of acetate ion at the anode with formation of an acetoxy radical, which subsequently would undergo decarboxylation with formation of methyl radicals as shown in Eqs. (14) and (15). 

Another approach to the problem involves the study of molecules in which one side is more accessible for adsorption than the other one. This feature is to a certain extent present in 2-t-butylindane which would be predicted to form substrate-electrode complex 15 preferentially. On anodic acetoxylation of 2-t-butyl-indane a mixture of cis- and r/vz s-l-acetoxy-2-t-butylindane in the proportions 16 84 is formed 106 Vhi all probability via a carbonium ion mechanism (Eq. 

Acyloxylation of aryl olefins probably involves radical cations as intermediates. Acetoxylation of frans-stilbene in anhydrous acetic acid/sodium acetate yields mainly meso-diacetate, while in moist acetic acid mainly threo-2-acetoxy-l,2-di-phenylethanol is formed 100 Anodic oxidation of trans- and ds-stilbene in ace-tonitrile/benzoic acid produces with both olefins the same mixtures of meso-hydrobenzoin diacetate (62) and f/ireo-2-benzoyloxy-l,2-dip]ienylethanol (63) l01 Product formation is best rationalized by a ECiqE-sequence leading to theienerge-tically most favorable acyloxonium ion (64) (Eq. (125) ) ... 

Fuchigami, Marken and coworkers also reported self-supported anodic methoxy-lation and acetoxylation of several aromatic compounds using a simple thin-layer flow cell reactor (interelectrode gap of 80 pm) (Scheme 4.41) [56]. The current efficiency (CE) of this process was 10% at best because of oxidation of methanol at flow rates lower than 0.03 ml/min. Even though CE increased at a faster flow rate (0.5 ml/min), the yield decreased sharply. The importance of selecting an appropriate choice of electrode material also was noted. 

A variety of alkylbenzenes undergo anodic acetoxylation, in which the loss of an a proton and solvation of the radical cation intermediate form the basis of side-chain and nuclear acetoxylation, respectively.30Sa b The nucleophilicity of the solvent can be diminished by replacing acetic acid with TFA. The attendant increase in the lifetimes of aromatic radical cations has been illustrated in anodic oxidations.308 Radical cations also appear to be intermediates in the electrochemical oxidation of alkanes and alkenes.309a-c... 

The same workers590,591 also showed that, in the Pd(II)-catalyzed acetoxylation of substituted arenes, a complete reversal of the usual pattern of isomer distribution for electrophilic aromatic substitution or anodic oxidation of aromatics is observed. To explain these results it was suggested that acetoxylation by Pd(OAc)2 takes place via the following addition-elimination sequence ... 

A general expression for anodic substitution reactions is shown in eqn (9). Here E is often hydrogen, but can also be another atom or group, e.g. t-butyl, OCH3, or COO- (this is the carbonium ion pathway of the well-known Kolbe reaction Eberson, 1968, 1973a). Examples of anodic substitution reactions include acetoxylation... 

In contrast, anodic cyanation of diphenylacetylene occurs exclusively at the aromatic ring and the triple bond remains intact 4-cyanodiphenylacetylenc is formed in 60% yield. The reaction was run at 2 V (vs. S.C.E.) for 3-9 F mol" using a platinum anode in methanol containing sodium cyanide. Anodic cyanation results in preferred attack at the aromatic nucleus in other systems toluene, mesitylene and hexamethylbenzene give nuclear substitution and little side-chain cyanation under similar conditions in contrast with the corresponding acetoxylation or methoxylation reactions. 

Eberson has compared the isomer ratios for the acetoxylation of aromatic substrates at the anode with those obtained from different oxidants (Table 1) [26]. The anodic reaction proceeds by an initial electron transfer, thus forming a radical cation, which is then attacked by acetate ion. The homogeneous reactions, which come closest to the results of the anodic oxidation, are the Co(III)Wi2O40 and the Ag(II) oxidation. These and also the Ce(IV) oxidant, which still exhibits some similarities in the isomer distribution, have been characterized as electron transfer oxidants, whereas the Pd(II)-catalyzed acetoxylation has been shown to proceed via organopalladium species [27]. The isomer distributions in the latter, where predominantly meta orientation is being observed, are drastically different from those of ET-mediated reactions. 

The situation in which the supporting electrolyte and/or the solvent is oxidized at a lower potential than the organic substrate is frequently encountered. Anodic methoxylation and cyanation are two typical cases for which homolytic processes involving methoxy and cyano radicals, respectively, have been invoked [125,126]. However, it can be shown that in cyanation [127-129] and at least some cases of methoxylation [130], one must work at an anode potential around or higher than the half-wave potential of the organic substrate in order to get any substitution product. Similar mechanism problems are apparent for the side-chain acetoxylation of alkylaromatic compounds in Ac0H-Me4NN03 [131,132]. 

A -Acylated amino acids are anodically oxidized in methanol or acetic acid solution under decarboxylative methoxylation or acetoxylation via the intermediate A-acyliminium ion in the course of a Non-Kolbe reaction (Hofer-Moest reaction) according to Scheme 8, path b. This type of reaction has been used intensively for amidoalkylation reactions by Mori, Seebach, and Steckhan. These reactions were based on the results of Iwasaki applying N-acyl aminomalonic acid half esters [Eq. (46)] [239]. 

Anodic acetoxylation of furan can be done in acetic acid containing acetate [173, 174] and benzoyloxylation in DMF containing benzoic acid and lithium chloride [175]. A mixture of cis- and ra 5-benzoyloxylated product is formed. Cyanomethoxylation of 2,5-dimethylfuran gives a mixture of cis- and rmn5-2-cyano-5-methoxy-2,5-dimethyldihydro-furan [176-178]. 

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