Alkoxylation by anodic

Ethers can be converted to acetals, and acetals to ortho esters, by anodic oxidation in an alcohol as solvent.194 Yields are moderate. In a similar reaction, certain amides, carbamates, and sulfonamides can be alkoxylated a to the nitrogen, e.g., MeS02NMe2 — Me-S02N(Me)CH20CH3.195 OS VII, 307. 

The direct electrochemical methoxylation of furan derivatives represents another technically relevant alkoxylation process. Anodic treatment of furan (14) in an undivided cell provides 2,5-dimethoxy-2,5-dihydrofuran (15). This particular product represents a twofold protected 1,4-dialdehyde and is commonly used as a C4 building block for the synthesis of N-heterocycles in life and material science. The industrial electroorganic processes employ graphite electrodes and sodium bromide which acts both as supporting electrolyte and mediator [60]. The same electrolysis of 14 can be carried out on BDD electrodes, but no mediator is required The conversion is performed with 8% furan in MeOH, 3% Bu4N+BF4, at 15 °C and 10 A/dm2. When 1.5 F/mol were applied, 15 is obtained in 75% yield with more or less quantitative current efficiency. Treatment with 2.3 F/mol is rendered by 84% chemical yield for 15 and a current efficiency of 84% [61, 62]. In contrast to the mediated process, furan is anodically oxidized in the initial step and subsequently methanol enters the scene (Scheme 7). 

Homolytic alkoxylation of olehns by anodic oxidation of alcohols gave products of which some were suggested to be formed through the intermediacy of the bridged positive ions (76) ... 

Anodic cyanation of alkoxylated biphenyls and other aromatic ethers is a limited but preparatively useful method for the formation of C-C bonds under mild conditions, as shown in Eq. (47) [103]. Mechanistic studies [104,105] supported a mechanism involving nucleophilic attack by cyanide ion on the aromatic radical cation rather than attack on the neutral aromatic nucleus by anodically generated cyano radicals, as had been proposed earlier [106]. 

Alkoxylation may be achieved by anodic oxidation in an alcohol, often methanol (MeOH), containing a suitable electrolyte, such as KOH, NaOMe, NaCN, NaBp4, or NH4NO3 [9-12,31,32]. Substrates that have been alkoxylated in this manner include aromatic compounds (both nuclear and side-chain alkoxylation has been observed), alkenes, ethers including vinyl ethers, enamines, N, AA-dialkylamines, AA-alkylsubstituted amides, and A-alkylsubstituted carbamates. In many cases alkoxylation by substitution is a side reaction only to concurrent alkoxylation by addition [7,9,11,33]. 

Both pyrrolizidine and indolizidine alkaloids can be synthesized by taking advantage of the anodic a-alkoxylation of Ai-alkoxycarbonylpyrroKdines (e.g. (131) to (132), Scheme 31). The method has been utilized to synthesize isoretronecanol (137), trachelanthamidine (138), elaeoka-nine A (135), and elaeokanine C (136) [57]. 

Since the extreme oxidizing power of the oxyl spin centers is successfully employed in waste water treatment, an application of these intermediates seems to be self-contradictory in terms of synthetic use. However, alkoxylation of hydrocarbons is a very important technical field since it allows the installation of functionalities without using the detour via halogenations. The selective introduction of functional groups on a completely nonactivated hydrocarbon has not yet been realized by BDD technology. In contrast, the direct anodic methoxylations of activated carbons exhibiting benzylic or allylic moieties can be performed at BDD anodes. The results obtained with BDD electrodes are quite similar to those when graphite serves as anode [57]. The anodic synthesis of benzaldehyde dimethyl ketals is industrially relevant and performed on the scale of several thousand tons. A detailed study of the anodic methoxylation of 4-tert-butyltoluene (10) at BDD was performed [58]. Usually, the first methoxylation product 11 and the twofold functionalized derivative 12 are found upon electrochemical treatment (Scheme 5). 

Both pyrrolizidine and indolizidine alkaloids can be synthesized by taking advantage of the anodic a-alkoxylation of A -alkoxycarbonylpyrrolidines (e.g., 83 to 84). The method, first developed by Ross, Finkelstein, and Petersen, and later explored by Ban and coworkers [24, 25], has been utilized by Shono s group to synthesize isoretronecanol (87), trachelanthamidine (88), elaeokanine A (89), and elaeokanine C (90) [26] (Scheme 7). Once the or-methoxy group has been installed via electrooxidation and nucleophilic capture of the intermediate by methanol, the product 84 is treated with enol ether 85 and titanium tetrachloride to affect C-C bond formation adjacent to nitrogen and afford 86. The latter served nicely in syntheses of both indolizidine alkaloids elaeokanine A (89) and C (90). 

Recently, Steckhan and coworkers [485,486] have reported that anodic methoxyla-tion of chiral 5-methyl- and 5-chloromethyl-2-oxazolidinones followed by Lewis acid-catalyzed allylation provides 4-allyl products highly diastereoselectively. Similarly, anodic methoxylation of cyclic dipeptides and dipeptolides derived from chiral a-amino acid [487] or a-hydroxy acid [488] provides useful chiral synthetic building blocks, as in Eq. (64). a-Alkoxylation of lactic amide derivatives was also reported [489]. However, the diasteros-electivity was low. 

It is necessary to mention that dining the development of metathetic approaches a number of aUcoxylating agents other than the alkali alkoxides have been tested in this purpose. For example, the gas phase co-condensation of volatile metal fluorides or chlorides with alkylsiliconalkoxides has been reported for the preparation ofM(OMc)6, M = Mo, W and Re (Jacob, 1982 Bryan, 1991). This technique requires a special equipment and provides rather small quantities of these products that can be obtained much more easily by the anodic oxidation of the corresponding metals. Another example of a different alkoxylating agent is the soluble Mg(OMe)2, which has been used to produce the methoxides from the metal fluorides (Bryan, 1991). 

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