Methoxylation anodic

A second type of anodic methoxylation is the Kolbe-type decarboxylation of A-acyl- or N-alkoxycarbonylamino acids in methanol. 

Optically active five- or six-membered cyclic A -acyliminium ions of this type are generated from the a-inethoxy derivatives, easily obtainable through anodic methoxylation of intermediates that are prepared via ex-chiral-pool syntheses from certain natural amino acids. Reaction of 5-substituted five-membered cyclic A -acyliminium ions with various nucleophiles leads to the predominant formation of cw-products with moderate selectivity. The trans-selective reaction with alkyl copper reagents appears to be an exception. 

Table 6. Efficiency of the anodic methoxylation and Hammett s a and

These facts indicate that an a-trifluoromethyl group remarkably promotes anodic substitutions with oxygen nucleophiles. Since these are very few successful examples of anodic methoxylation of phenylalkyl sulfides are known, it is notable that an a-trifluoromethyl group facilitates the anodic methoxylation. Therefore, such anodic substitutions have been systematically investigated from both mechanistic and synthetic aspects [42]. 

Table 7. Anodic methoxylation and acetoxylation of fluoroaikyl phenyi sulfides...

When the anodic fluorination of 2-monofluoroethyl sulfide 5 is carried out in methanol containing Et3N-3HF instead of acetonitrile as a solvent, interestingly the a-methoxylated product 7 rather than the a-flourinated product 6 is obtained exclusively (Scheme 6.10) [51]. As described above, 7 is not obtained from 5 under conventional anodic methoxylation conditions. Therefore, that this novel fluoride ion promoted anodic methoxylation is remarkable. As shown... 

Table 9. Fluoride ion promoted anodic methoxylation of fluoroalkyl sulfides...

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. 

In contrast to the cathodic reduction of organic tellurium compounds, few studies on their anodic oxidation have been performed. No paper has reported on the electrolytic reactions of fluorinated tellurides up to date, which is probably due to the difficulty of the preparation of the partially fluorinated tellurides as starting material. Quite recently, Fuchigami et al. have investigated the anodic behavior of 2,2,2-trifluoroethyl and difluoroethyl phenyl tellurides (8 and 9) [54]. The telluride 8 does not undergo an anodic a-substitution, which is totally different to the eases of the corresponding sulfide and selenide. Even in the presence of fluoride ions, the anodic methoxylation does not take place at all. Instead, a selective difluorination occurs at the tellurium atom effectively to provide the hypervalent tellurium derivative in good yield as shown in Scheme 6.12. 

The reaction proceeds via electrogenerated cationic species as its seen with the nonfluorinated amines, carbamates, and amides (Scheme 6.14). However, the regiochemistry of this anodic methoxylation is not governed by the stability of the cationic intermediates B and B (thermodynamic control) since the main products are formed via the less stable intermediates B. Indeed, this remarkable promotion effect and unique regioselectivity can be explained mainly in terms of a-CH kinetic acidities of the cation radicals formed by one-electron oxidation of the amines since the stronger the acidity of the methylene hydrogen, the easier the deprotonation. 

The solute-solvent mixture in electroor-ganic conversions frequently is not conductive enough and a supporting electrolyte has to be added. If an acidic or basic reaction medium is used, the needed acid or base may be sufficient to increase the conductivity of the electrolyte. This is an inexpensive way, and after the reaction, mostly a simple neutralization is possible. If in special cases a mediator is applied - for example, a bromide for the industrial anodic methoxylation of fu-ran [57] - this can provide an adequate conductivity. 

Scheme 2 Anodic methoxylation of / -methylstyrene without and with an amine radical cation as mediator.

Both anodic oxidation reactions proceeded well. As illustrated in Scheme 44, an anodic methoxylation of menthyl pyroglutamate followed by the trapping of an incipient A-acyliminium ion with allyl-silane in the presence of Lewis acid led to (138) [86]. While the stereoselectivity of this reaction was not high, the major product from the reaction could be fractionally crystallized from hexane and the route used to conveniently prepare (138) on a scale of 10 g. In this case, a platinum wire anode was used in order to keep the current density high. This was required because of the high oxidation potential of the secondary amide relative to the methanol solvent used in the reaction. 

J. S. Swenton, Anodic methoxylation of aromatic compounds occurring via the EECrCp... 

CH bonds a to an amino group Anodic methoxylation of unsymmetrical tertiary amines takes place preferentially at the methyl group (Fig. 6) [28-30]. Substitution at a CH bond a to an amino group proceeds by oxidation of the amino group to a radical cation, followed by deprotonation at the adjacent CH bond to a radical. This is oxidized to a cation, which undergoes solvolysis, in this case, methanolysis. The regioselectivity has been explained by assuming that an adsorbed amine from which the intermediate cation is formed is as distant as possible from the anode... 

A different regioselectivity has been reported in the anodic methoxylation of A-(fluoroethyl) anilines as shown in Fig. 9 [33]. Since in this case, the regioselectivity decreases with the decreasing electron-withdrawing ability of the Rf groups (—I-effect), it can be explained in... 

Direct anodic methoxylation of biscarba-mates of a methyl a, tu-diaminocarboxylate... 

Fig. 10 Regioselective anodic methoxylation of unsymmetrical carbamates using electroauxiliaries [36, 37].

Anodic methoxylation of conformation-ally biased 2-substituted At-acyl piperidines leads regioselectively to 6-methoxy products owing to the steric constraints... 

Chemoselective anodic methoxylation at a distinct carbon atom in the a-position to an amino group in a polypeptide was achieved by prior introduction of a silyl group as an electroauxiliary at this carbon atom [156]. Amide oxidation in A-acetylpyrrolidines substituted with electron-rich phenyl rings led to either methoxylation a to the nitrogen atom or in the benzylic position. Mechanistic studies indicate that both the amide and the phenyl oxidation compete, but intramolecular electron transfer leads to... 

Hydroxypiperidine alkaloids have been synthesized via anodic methoxylation that allowed the regio- and stereoselective introduction of substituents [213]. A highly diastereoselective fluorination was achieved with chiral l,3-oxathiolan-5-ones derived from camphorsulfonamide. In dimethoxyethane containing Et4NF-4HF, the monofluorinated product (9) was obtained as a single diastereomer [214]. 

Alipathic cyclic olefins form the fr ns-dimethoxy compound in anodic methoxylation however, only as a minor... 

Urethanes can be anodically methoxylated, as other amides they may react with furan in the presence of an acid. Anodic methoxylation of the furan gives a dimethoxydihydrofuran in the Clauson-Kaas reaction1 on acid hydrolysis 3-hydroxypyridines (51) are obtained114 [Eq. (46)]. 

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