Electrochemical alkoxylations

Aromatic ethers and furans undergo alkoxylation by addition upon electrolysis in an alcohol containing a suitable electrolyte.Other compounds such as aromatic hydrocarbons, alkenes, A -alkyl amides, and ethers lead to alkoxylated products by substitution. Two mechanisms for these electrochemical alkoxylations are currently discussed. The first one consists of direct oxidation of the substrate to give the radical cation which reacts with the alcohol, followed by reoxidation of the intermediate radical and either alcoholysis or elimination of a proton to the final product. In the second mechanism the primary step is the oxidation of the alcoholate to give an alkoxyl radical which then reacts with the substrate, the consequent steps then being the same as above. The formation of quinone acetals in particular seems to proceed via the second mechanism. ... 

Intramolecular electrochemical alkoxylation of racemic l-(3-hydroxybu-tyryl)piperidine afforded a diastereomeric mixture of 2-methylperhydropyr-ido[2,l-Z)][l,3]oxazin-4-ones (OOMIl 1). 

The reaction proceeds with high regioselectivity for oxidation at the less substituted a-carbon. Methanol is commonly used as the solvent, although higher alcohols are also used for some detailed experimental procedures refer to the literature60,61. Some examples of compounds prepared via electrochemical alkoxylation are ... 

For dissociative electron transfer, an analogous thermochemical cycle can be derived (Scheme 2). In this case the standard potential includes a contribution from the bond fragmentation. Using equations (40) and (41) one can derive another useful expression for BDFEab-, equation (42). While direct electrochemical measurements on solutions may provide b. b, for example, of phenoxides and thiophenoxides (Section 4), the corresponding values for alkoxyl radicals are not as easily determined. Consequently, these values must be determined from a more circuitous thermochemical cycle (Scheme 3), using equation (43). The values of E°h+/h io a number of common solvents are tabulated elsewhere. Values of pKa in organic solvents are available from different sources. " A comparison of some estimated E° values with those determined by convolution voltammetry can be found in Section 3. 

Highly selective formation of phenyl acetate was observed in the oxidation of benzene with palladium promoted by heteropoly acids.694 Lead tatraacetate, in contrast, usually produces acetoxylated aromatics in low yields due to side reac-tions. Electrochemical acetoxylation of benzene and its derivatives and alkoxylation of polycyclic aromatics789 790 are also possible. Thermal or photochemical decomposition of diacyl peroxides, when carried out in the presence of polycyclic aromatic compounds, results in ring acyloxylation.688 The less reactive... 

Abstract Boron-doped diamond (BDD) electrodes provide an unusually wide electrochemical window in protic media, since there exist large offset potentials for the evolution of molecular hydrogen and oxygen, respectively. At the anode, alcohols are specifically converted to alkoxyl radicals. These can be used for chemical synthesis. When the enormous reactivity of such intermediate spin centers is not controlled, mineralization or electrochemical incineration dominates. Efficient strategies include either high substrate concentrations or fluorinated alcohols which seem to stabilize the spin centers in the course of reaction. 

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). 

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). 

The discovery of a different reaction mechanism of anodic methoxylations on BDD electrodes led to a closer investigation of electrosynthetic possibilities. First of all, BDD electrodes exhibit a 400- mV larger electrochemical window in methanol compared with graphite (Fig. 5.4). This opens access to a series of alkoxylation reactions which are not selective on conventional electrodes. 

Moeller and coworkers [484] found that electrochemical cyclization (anodic intramolecular alkoxylation) of optically active dipeptides proceeded highly diasteroselectively. 

A spatially addressable electrolysis platform has been used for parallel electrosynthesis. For example, the anodic a-alkoxylation of carbamates and sulfonamides is carried out using a Teflon block with 16 wells and a set of 16 glass vials under the constant-current conditions to obtain the corresponding products in a parallel fashion (Fig. 1) [4]. The parallel electrosynthesis can also be applied to reduction. The electrochemical reductive hydrocoupling of aldimines using sacrificial A1 anodes gives the corresponding 1,2-diamine derivatives [5]. 

Electrochemical generation of fiillerene cation radicals has not been used for synthetic purposes yet. 50 cation radicals, formed by chemical oxidation in protic superacidic media, can be easily trapped with alcohols, aromatics, and x,y-diols to form alkoxylated or arylated fullerenes and difiilleroxyalkanes (earmuff ethers) respectively [92]. 

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