Patai S., Rappoport Z. 1997 The chemistry of functional groups. The chemistry of double-bonded functional groups / 0611 640

One of the primary issues in the electrochemical reduction of any carbonyl compound is the nature of the electroactive species under a particular set of experimental conditions, of which the proton donor ability of the solvent is paramount. The behavior of diaryl ketones is best understood in this respect. In acidic media (pH < 5), the species undergoing reduction is the protonated carbonyl compound (41) and the reduction affords a neutral ketyl radical (42). Dimerization of the latter affords benzpinacols, which generally rearrange to benzpinacolones under the acidic reaction conditions. In neutral and weakly basic media (pH from 5 to 11), the neutral carbonyl compound is reduced to a radical anion (43), which is protonated rapidly; the resulting ketyl radical usually immediately accepts a second electron and proton, and the product is the secondary alcohol. Reduction in strongly basic or aprotic media affords 43, which dimerizes to a pinacol. Aryl alkyl ketones and aldehydes have been generally believed to exhibit similar behavior (but see next paragraph). Dialkyl ketones and aliphatic aldehydes are not reducible at all under aprotic conditions; the LUMO of these substances is apparently too high to be accessible. These compounds are however reducible in protic media, e.g. alcohol solvents. Under these conditions the electroactive species is probably an alcohol carbonyl hydrogen-bonded complex. These types of compounds are generally reduced to alcohols; the intermediate ketyl radical is apparently reduced to an anion (44) at the very negative potentials at which reduction must be carried out, and protonation of 44 to afford the alcohol is undoubtedly fast.

Attention has turned recently to the mechanistic details underlying these processes. Probably the most significant development in this area in recent years is the discovery that the ketyl radical produced by electrochemical reduction of benzaldehyde in buffered neutral ethanol is harder to reduce than benzaldehyde itself46. All previous discussions had assumed that the ketyl radical would be reduced as quickly as it is formed, but fast scan cyclic voltammetry demonstrated the existence of a short-lived intermediate, apparently the ketyl radical. Computer simulation of the voltammograms showed that the radical dimerizes at a rate ca 106 M 1 s 1.

Many aliphatic aldehydes exist primarily as hemiacetals in alcoholic solvents. It has been well understood for many years47 that the actual reducible species, or ‘electrophore’, in such media is not the hemiacetal but rather the small amount of the carbonyl compound itself (actually a hydrogen-bonded complex; see above) present at equilibrium. Thus reduction is kinetically controlled; that is, the overall rate of reduction is governed by the rate of conversion of the hemiacetal to the aldehyde. More recently, this has been confirmed and studied for formaldehyde and acetaldehyde in water at different pH levels48 and the kinetics of the reduction process have been studied for glucose, galactose and lactose49.

Synthetically, the question of which product is formed from a given carbonyl compound, the pinacol or the alcohol, is obviously of great interest. We have already noted the critical importance of the proton-donating ability of the medium in this respect. Attention has turned to the effect of other variables on the pinacol/alcohol ratio. Formaldehyde can be reduced cleanly to ethylene glycol at an electrode composed of a special type of carbon, in a process of potential commercial significance50. Nonaka and coworkers have found that reduction of aldehydes proceeds more selectively to aldehydes at nickel Teflon silica gel composite electrodes51. Nonaka and coworkers have also shown that for aromatic

O

X

( )n ( )m

(50)

2. Carboxylic acids and acid derivatives

Carboxylic acids cannot normally be reduced directly electrochemically1; they can however be reduced to aldehydes by electrolysis in an undivided cell containing tributylphosphine and methanesulfonic acid72. The conversion involves an interesting combination of anodic and cathodic reactions (Scheme 9).

(stable)

SCHEME 9

Aroyl chlorides undergo an interesting electrochemical reduction to afford 1,2- dibenzoyloxystilbenes (54)73 75. The reaction appears to involve reductive dimerization to benzil (52) (Scheme 10). The latter is readily reduced to a stilbenediolate (53). Reaction of 53 with unreacted aroyl chloride affords 54 (trans:cis D 2 : 1). Alkene 54 can be further reduced to a diphenylacetylene by electrolysis at a more negative cathode potential74. Benzoyl fluoride undergoes the same conversion to 5474. Voltammetric investigations and careful product analysis have revealed the fact that these reactions are actually more complex than suggested by Scheme 10. Typically, at least two voltammetric waves are observed74,75. The most positive is that of the acid chloride itself. A second wave is usually seen for the corresponding benzaldehyde. Small amounts of the corresponding aldehyde also accompany 54 in the preparative electrolysis. Other electrolysis products include the corresponding carboxylic acid and anhydride; these presumably arise by reaction of the acid chloride with traces of moisture in the solvent74,75. Electrolysis of thiophene- 2-carbonyl chloride in the presence of D2O and CD3CN gave products suggesting the intermediate formation of the benzoyl anion75b. Reduction of phthaloyl chloride affords 55 in 65% yield76. In this system, the enediolate intermediate is trapped intramolecularly (Scheme 11). On the other hand, electrochemical reduction of terephthaloyl chloride (para-substituted) and its derivatives affords linear polyterephthaloylenes in good yield (95% for the parent compound)77.

Reduction of aliphatic acid chlorides follows a roughly similar course78. That is, tetrameric products similar to 54 are the major products, together with small amounts of the corresponding aldehyde. The latter has been suggested to be formed from both acyl radical

would take a different course because of the better leaving group ability of bromine.

(30)

O O

The electrochemical reduction of acid chlorides takes a very different course when carried out in an undivided cell equipped with nickel cathode and anode79. The product is a symmetrical ketone (57); 57 is formed by a complex sequence involving both electrodes (Scheme 12). This is really a chemical reaction induced by a highly reactive form of nickel produced by dissolution of the anode and plated onto the cathode. We have already encountered similar chemistry involving highly reactive zinc (Section V.A.1).

SCHEME 13

Esters undergo conversion to 1,2-diketones when reduced in a cell containing a magnesium anode80. Reduction in the presence of chlorotrimethylsilane affords an enediol bis-silyl ether (Scheme 13)80. Coordination of the chlorosilane probably activates the diketone for reduction80. The effect of the magnesium anode is less clear; coordination of magnesium ion to the diketone may stabilize it against further reduction; magnesium ions

liberated at the sacrificial anode can presumably also facilitate reduction of the starting ester. This interpretation is bolstered by work of Pletcher and Slevin81, who showed that in DMF benzoate esters undergo alkyl-oxygen cleave to afford benzoate ion, whereas coupling is fast in the presence of added magnesium ion81. The role played by experimental conditions on these reactions still leaves much to be resolved. Thus, electrochemical reduction of esters and N, N-dialkyl amides takes a very different course when carried out in a t-BuOH/THF mixture in a cell containing magnesium anode and cathode; the ester is reduced to the primary alcohol stage82. Substitution of t-BuOD results in formation of RCD2OH from RCO2R0 . Ring-opening is observed with amide 5883, the isomerization of which to 61 is initiated electrochemically, but for which there is no net consumption of current (Scheme 14).

SCHEME 14

The electrochemical reduction of 2,6-pyridine diesters and S-thioesters shows interesting contrasts. The first step in each case is conversion to a short-lived radical anion, but the esters undergo alkyl-oxygen cleavage (cf Reference 81), whereas the S-thioesters undergo cleavage of the C(O) S bond84. The latter mode of cleavage is reasonable, inasmuch as S-thioesters resemble acid chlorides chemically more than they do esters.

3. 1,2-Dicarbonyl compounds

1,2-Diketones are easily reduced electrochemically because of the mutual electronwithdrawing effect of one carbonyl group on the other. Two-electron reduction usually takes place to afford an enediolate (62), which can then react with an electrophile E present in the medium (equation 31; see also Schemes 10 and 13); an alpha-hydroxy ketone is formed by subsequent tautomerization when E D H1,85,86. An unusual exception to the generalization that these substances undergo two-electron reduction is the electrochemical behavior of acenaphthenequinone (63), which is converted to the expected enediol dibenzoate (64) in the presence of aroyl chlorides but affords the dimeric substance 65 (shown to be the meso diastereomer by X-ray crystallography) in the presence of acetic

OAc

O

2

(65)

SCHEME 15

Schafer¨ examined the effect of chiral auxiliaries on the stereochemistry of reduction of a series of ˛-ketoamides (equation 32)88. Diastereomeric excesses ranged from 42 to 81%.