Electrochemical pinacolization

Lagrost C, Hapiot P, Vaultier M (2005) The influence of room-temperature ionic liquids on the stereoselectivity and kinetics of the electrochemical pinacol coupling of acetophenone. Green Chem 7(6) 468-474... 

Electrochemical reduction of carbon-fliionne bonds occurs at high pH when a carbonyl group is adjacent Polaiographic reduction of a a,a-tnfluoroacetophe-none without loss of fluonne predominates in acidic media to give the alcohol and the corresponding pinacol, whereas reduction of the unprotonated ketone results in hydrogenolysis of the tnfluoromethyl group to form acetophenone as product Il] (equation 8)... 

Reductive dunenzation to form fluorinated benzopinacols proceeds m the partly fluormated case either with zinc or by photolysis but is not observed with perfluorobenzophenone [651 (equation 53). Trifluoroacetophenone is reduced electrochemically in dimethylformamide to a stable radical anion, which, m the presence ot lithium ion, rapidly dunerizes to pinacol in higher yield than that available by photoreduction [66] (equation 54)... 

A number of useful reviews have appeared in the course of the last few years, and a number of chemicals, such as vitamin C, p-tetralone, hexafluoropropylene oxide, piperidine, glyoxalic acid, pinacol, p-hydroxypropiophenone, sebacic acid, p-anisaldehyde, maltol/ethyl maltol. Rose oxide, linalool, perfluorooctanoic acid, hydroquinone, etc., that are commercially made (or can be made) electrochemically have been catalogued. 

Low-valent lanthanides represented by Sm(II) compounds induce one-electron reduction. Recycling of the Sm(II) species is first performed by electrochemical reduction of the Sm(III) species [32], In one-component cell electrolysis, the use of sacrificial anodes of Mg or A1 allows the samarium-catalyzed pinacol coupling. Samarium alkoxides are involved in the transmet-allation reaction of Sm(III)/Mg(II), liberating the Sm(III) species followed by further electrochemical reduction to re-enter the catalytic cycle. The Mg(II) ion is formed in situ by anodic oxidation. SmCl3 can be used in DMF or NMP as a catalyst precursor without the preparation of air- and water-sensitive Sm(II) derivatives such as Sml2 or Cp2Sm. 

Arylalkyl and diaryl ketones are converted to the corresponding pinacols upon electrochemical reduction in acidic and very alkaline media ... 

In a number of other cases it has been reported or implied that a single diastereomeric pinacol was formed, but the stereochemistry of the product was not determined these reports come from studies upon the electrochemical reduction of 3-acetylpyridine 87), p-acetamidobenzaldehyde 9I>, (3-di-methylaminopropiophenone 91 p-aminoacetophenone (which affords one pinacol in acid and the other in alkali)92), and the reduction of a mixture of p-dimethylaminoacetophenone and p-methoxyacetophenone to afford a mixed pinacol (87) 93>. 

In view of the very considerable activity in this area it is surprising and somewhat dismaying to find that relatively little attention has been paid to the identity of the electrochemically generated pinacols. In none of the studies cited in the preceding paragraph was the stereochemistry of the products estab-... 

The reduction of ketones to pinacols can also be achieved electrochemically via ketone anion radicals that are observable as transient intermediates.45... 

Durandetti et al. have described iron-catalyzed electrochemical allylation of carbonyl compounds with allylic acetates (Equation (27)).333 In the case of aldehydes, slow addition of the corresponding aldehyde is required in order to avoid pinacol formation. With crotyl acetate (R3 = Me), the reaction proved to be highly regioselective, providing almost exclusively branched homoallylic alcohols 150. 

The shape of this wave and the variation with pH are both consistent with fast equ-librium reactions In the pH region lower than the value of pK, for the hydroxyl radical, the reactions of this hydroxyl radical dominate the electrochemical process. Controlled potential reduction at the potential of this first wave indicates a IF process and the principal products are dimers of the hydroxyl radical. The second wave in this acidic region is due to addition of an electron and a proton to the neutral radical. This process competes with dimerization in the mid-pH range where the two polarographic waves merge. Over the pH range 7-9, monohydric alcohol is the principal product. At pH <3 or >12, pinacols are the main products. Unsymmet-rical carbonyl compounds afford mixtures of ( )- and meso-pinacols. Data (Table 10.3) for the ( ) / meso isomer ratio for pinacols from acetophenone and propio-phenone indicate different dimerization mechanisms in acid and in alkaline solutions. 

Bimolecular reduction of ketones has also been recorded. Thus electrochemical reduction of the ketones (378) gave the pinacols (379) <74CR(C)(279)779,74CR(C)(279)25>. 

Several studies have been made of the effect of added metal ions on the pinacol/alcohol ratio. Addition of antimony(m) chloride in catalytic amounts changes the product of the electrochemical reduction of acetophenone in acidic alcohol at a lead electrode from the pinacol in the absence of added metal salt to the secondary alcohol in its presence53. Antimony metal was suspected to be an intermediate in the reduction. Conversely, addition of Sm(in) chloride to DMF solutions of aromatic aldehydes and ketones54 and manganese(II) chloride to DMF solutions of hindered aromatic ketones55 results in selective formation of pinacols in excellent yields. When considering these results one should keep in mind the fact that aromatic ketones tend to form pinacols in DMF even in the absence of added metal ions1,29,45. 

The reduction of carbonyl compounds to form pinacol dimers can be accomplished photochemically, electrochemically or with chemical reducing agents. When conducted under acidic conditions or in protic solvents, pinacols are likely produced by coupling of two neutral ketyl radicals (vs radical anions). The electrochemical reduction is especially complicated in terms of the role of the electrode surface, counterion and solvent, and an excellent review has appeared on the subject32. 

Inokuchi, Kusumoto and Torii reported the electrochemical reduction of epoxyketone 29 at a carbon cathode (equation 16)62. In the absence of a proton source, two deoxygenated products (enone 30 and pinacol dimer 31) were produced in a combined yield of 37%. However, in the presence of a proton source (CH2(CC>2Et)2), ring-opened product 32 was produced in 65% overall yield. 

Pinacol condensation.1 This reaction can be effected with stoichiometric amounts of SmX2, which is not available commercially. The same reaction can be carried out with SmCl3, a stable and relatively inexpensive lanthanide, in catalytic amounts (5-10%) if conducted as an electrochemical reaction. Evidently, electrosynthesis can regenerate the divalent active species. 

The corresponding methyl hetaryl ketones are much less hydrated,285,266 as would be expected, and their electrochemical behavior resembles more that of acetophenone. Depending on pH, the products are the pinacols, the carbinol, or mixtures thereof207-269 in acid solution mostly carbinols, at high pH mostly pinacols, are formed. The proportion of + -pinacol to meso-pinacol obtained in the electrolytic reduction of 2-acetopyridine is, however, different from that from acetophenone.2fl8,269 The /meso ratio in alkaline solution is about 2.8 for acetophenone and about 0.3 for 2-acetopyridine. 

Although chlorosilanes are an obvious choice as mediators for catalysis on account of their high affinity for oxygen, low price and lack of toxicity, several other additives can also be envisaged. The recent publication on the electrochemical version of the Nozaki reaction mentioned above simply employs the Li cations of the supporting electrolyte for this very purpose [15], whereas another titanium-catalyzed pinacol... 

Reduction of ketones. Saturated and conjugated ketones can be reduced by the reagent to alcohols, probably by a mechanism similar to electrochemical reduction (as illustrated for acetophenone in scheme I). In some cases, ptnacols are formed as well. Thus acetophenone is reduced to the alcohol (45 % yield) and the pinacol (45% yield). Generally the alcohol is the predominant product. For example, benzophenonc is reduced to benzhydrol in 98 % yield. a,)3-Unsaturated ketones are reduced to saturated alcohols. Reduction of camphor gives predominantly the exo-alcohol note that reduction with sodium in alcohol or with potassium, in the presence of graphite (not intercalated), gives predominantly the endo-alcohol. 

The electrochemical reduction of a,p-unsaturated ketones and related compounds in aprotic media in the absence of metal cations can, in some cases, lead to relatively stable anion radicals.However, in the presence of proton donors the latter are protonated to form hydroxyallyl radicals, which tend to dimerize more rapidly than they diffuse back to the electrode to undergo further reduction (Scheme 17). Although these allyl radicals prefer to dimerize by coupling at the -position, if this position is sterically hindered, as in the case of cholest-4-en-3-one, coupling at the carbonyl carbon may be observed, yielding pinacols. ... 

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