Electrosynthesis of Ketones

The anodic oxidation of secondary alcohols to the corresponding ketones is generally inferior to the catalytic dehydrogenation methods. Electrochemical syntheses are therefore of interest only in special cases. An example of this is the regioselective oxidation of an endo-hydroxyl group in 1,4,3,6-dianhydrohexitols 306)  

The nickel oxide anodexan also be used in the oxidation of secondary alcohols but frequently has no advantage over catalytic processes  

---

Table 19. Electrosynthesis of ketones from organic halides and carbon monoxide...

The electrosynthesis of bicyclic ketones (198) has been performed by the reduction of bromoalkylcyclohexenones using Ni(II) complexes as mediators. The electrochemical Michael-type addition (197) (198) can be attained in a DMF-NH4Cl04/Et4NCl04-(C/C) system in the presence of Ni(cyclam)(Cl04)2 as a redox mediator at —1.8 V (SCE) (Scheme 77) [308]. 

The Barhier-type reaction of aldehydes and ketones with allyl halides (485) in the presence of Sml2, leading to homoallyl alcohols (486), has received recent interest as a one-step alternative to the Grignard reaction. However, the reactions require the use of stoichiometric amounts of the reducing Sm(III) species. Recently, the electroreductive Barhier-type allylation of carbonyl compounds in an SmH-mediated reaction has been developed [569]. The electrolysis of (485) is carried out in a DMF-SmCl3-(Mg/Ni) system in an undivided cell to give the adduct (486) in 50 85% yields (Scheme 168) [569]. Electrosynthesis of y-butyrolactones has been achieved by the reductive coupling of ethyl 3-chloropropionate with carbonyl compounds in the presence of a catalytic amount of SmCfi [570]. 

Tilborg and coworkers " recently reported an extensive study concerning the electrosynthesis of cyclopropanone adducts from either a,a -dibromo ketones or from a,a -dibromo- and a,a -dichloro-carbonyl protected ketones. With the non-protected ketones the reductions were carried out in MeCN in the presence of various nucleophiles (Table 2). It was found that the yields of cyclopropanone adducts decrease when the dihaloketone becomes less substituted, due to a competing side reaction in which a bromide is displaced by the nucleophile. Furthermore, in the presence of excess of added protic nucleophile the yields of the cyclic products decrease due to a competing protonation of the anionic intermediate. 

Recently, Belot and coworkers reported the electrosynthesis of mono- and dicyclopropyl carbonyl derivatives from the electrolysis of aromatic ketones and their corresponding SchifF bases in the presence of X(CH2)3COCl (X = Br, Cl). Moderate yields, which depended on the solvent and other experimental conditions, were obtained. 

The halogen-mediated in-cell oxidation of ketones is a recently commercialized electrosynthesis. 

H Putter, J Botzem, H Hannebaum, D Hermeling. Electrochemical Methoxylation of Ketones. 12th International Fonim on Electrolysis in the Chemical Industry. Clearwater, FL Electrosynthesis Company, October 11-15, 1998. 

Reductions. Sm(II) has been developed as a versatile one-electron reductant of broad utility in organic synthesis. Sm(II) can be prepared and regenerated in situ by reduction of Sm(III) in DMF with a consumable magnesium anode (52-54), Under these conditions aromatic esters are reductively dimerized to 1,2-diJketones with only 10% Sm(III) (52). Similarly, allylic chlorides can be added to ketones to give homoallylic alcohols (55). SmCl3-catalyzed electrosynthesis of y-butyrolactones from 3-chloro esters and ketones or aldehydes proceeds in 25-76% yield (54). 

Iron was among the metals, used in the electrosynthesis of a wide range of alcohols from organic halides and ketones or aldehydes (see Sect. 2.4 and 3.4... 

Pienemann T, Sch er H-J (1987) Reductive amination of ketones and aldehydes at the mercury cathode. Synthesis 1987 1005-1007 Gomez JRO (1991) Electrosynthesis of N-methylhydroxylamine. J Appi Eiectrochem 21 331-334... 

Paired Electrosynthesis, Fig. 7 Linear electrosynthesis of methyl ethyl ketone from 2,3-butanediol... 

Intermediate enols can also be oxidized by indirect electrosynthesis (vide supra) halide anions are used as oxidation mediators. A multistep reaction converts ketones into a-hydroxylated acetals when oxidized electrochemically in the presence of iodine as the redox catalyst (Scheme 48) [196],... 

Some aspects of the mechanism of the Kolbe reaction are still very much a matter for debate as in some respects is the mechanism of electroreduction of aldehydes and ketones key questions appear to be the nature of the intermediates and if they are adsorbed or not. It has been well established " that in aqueous electrolytes the Kolbe reaction does not occur below a certain critical anodic potential (--1.9 V vs. normal hydrogen electrode). The results of a thorough study of this electrosynthesis in both aqueous and anhydrous systems were interpreted in terms of adsorbed carboxyl radicals. With increasing anodic potential, these intermediate species gradually cover the electrode surface until discharged to a second adsorbed radical at anode potentials above the critical potential. Subsequent dimerization and desorption occurs to yield the product hydrocarbon ... 

The selective oxidative phenolic orf/io-coupling reaction of simple methyl-substituted phenols turned out to be challenging [12]. When 2,4-dime thy Iphenol (1) is treated by conventional or electro-organic methods, not only the desired biphenol (2) is formed but rather a plethora of polycyclic architectures (Scheme 2) is observed. The major product is Pummerer s ketone (3) and related compounds with a wide structural diversity [13-16]. Application of a boron tether ameliorated the situation tremendously, and biphenol (2) was obtained as the major product [17, 18]. This templated anodic oxidation of 1 represents a multistep process but is suitable for the electro-organic synthesis of (2) on larger scale (see entry Electrosynthesis Using Template-Directed Methods ) [19]. 

The examples illustrate the diversity as well as the common features of a paired electrosynthesis. One can start with one or two substrates to generate one or two products. Electrode processes can be mediated or direct. Undivided and divided cells are employed in paired electrosyntheses. But as in the BASF phthahde example, it is crucial for the synthesis of glyoxylic acid, sorbitol, and methyl ethyl ketone that the cathodic process is the reduction of the substrate and not the reduction of protons because in these cases protons are generated at the anode and the electrolysis takes place in aprotic solvent. Therefore effects that minimize the overpotential of hydrogen have to be omitted. Reaction control is important in all described examples, and consequently the cell and the setup have to fit for each case. Work-up and product isolation are significant for a successful synthesis and can be even more challenging in a paired synthesis. 

---