Ketones electroreduction

Attempted intermolecular coupling of ketones and nitriles under conditions similar to those used for intramolecular coupling led to mixtures of two types of ketone-nitrile coupling products and alcohols resulting from ketone electroreduction. Product selectivity could be changed altering nitrile/solvent (2-propanol or ethanol) composition. Some results for cyclohexanone/acetonitrile reductions are shown in Scheme 27. 

In this section primarily reductions of aldehydes, ketones, and esters with sodium, lithium, and potassium in the presence of TCS 14 are discussed closely related reductions with metals such as Zn, Mg, Mn, Sm, Ti, etc., in the presence of TCS 14 are described in Section 13.2. Treatment of ethyl isobutyrate with sodium in the presence of TCS 14 in toluene affords the O-silylated Riihlmann-acyloin-condensation product 1915, which can be readily desilylated to the free acyloin 1916 [119]. Further reactions of methyl or ethyl 1,2- or 1,4-dicarboxylates are discussed elsewhere [120-122]. The same reaction with trimethylsilyl isobutyrate affords the C,0-silylated alcohol 1917, in 72% yield, which is desilylated to 1918 [123] (Scheme 12.34). Likewise, reduction of the diesters 1919 affords the cyclized O-silylated acyloin products 1920 in high yields, which give on saponification the acyloins 1921 [119]. Whereas electroreduction on a Mg-electrode in the presence of MesSiCl 14 converts esters such as ethyl cyclohexane-carboxylate via 1922 and subsequent saponification into acyloins such as 1923 [124], electroreduction of esters such as ethyl cyclohexylcarboxylate using a Mg-electrode without Me3SiCl 14 yields 1,2-ketones such as 1924 [125] (Scheme 12.34). 

The electroreduction of aldehydes and ketones often involves the formation of dimeric hydroxy derivatives—pinacols ... 

Nickel-bpy and nickel-pyridine catalytic systems have been applied to numerous electroreductive reactions,202 such as synthesis of ketones by heterocoupling of acyl and benzyl halides,210,213 addition of aryl bromides to activated alkenes,212,214 synthesis of conjugated dienes, unsaturated esters, ketones, and nitriles by homo- and cross-coupling involving alkenyl halides,215 reductive polymerization of aromatic and heteroaromatic dibromides,216-221 or cleavage of the C-0 bond in allyl ethers.222... 

The complex [Ni(bpy)2]2+ catalyzes the electroreductive coupling of organic halides and carbon monoxide into ketones under a CO atmosphere,226 or in the presence of a metal carbonyl,227 especially iron pentacarbonyl. Unsymmetrical ketones have been obtained from mixtures of two different organic halides.228 CO is very reactive towards reduced Ni° species to form the stable [Ni°(bpy)(CO)2]° complex, which probably evolves to a transient arylnickel [Nin(bpy)(R)(CO)X]° complex in the presence of both ArX and [Ni°(bpy)]° species.229,230... 

Table 2.9 Electroreductive coupling of ketones with nitrones...

The same electrochemical process was also used for the coupling between aldehydes or ketones and activated alkyl halides such as a-chloroesters, -nitriles, and -ketones as well as aya-dichloroesters.334 Electroanalytical studies have shown initial electroreduction of Fe(n) to Fe(i) and subsequent formation of an iron organometallic intermediate (e.g., a 7t-allyliron complex in Equation (27)) before reaction with the corresponding carbonyl compounds.335... 

Electroreduction of aliphatic amides in the presence of chlorotrimethylsilane gives coupling products and this reaction is useful for the synthesis of a-amino ketones (Scheme 22) [41]. In this reaction, the formation of an Mg salt promotes the coupling of two anion radical centers. 

Reduction potenhals of ketones and aldehydes are effected by the substituents. Electron-withdrawing groups usually facilitate the electroreduction of these compounds [1, 2]. Electroreduction of aliphatic and aromatic ketones and aldehydes generally takes place under mild reaction conditions however, the nature... 

Since the electroreduction of ketones shown in Scheme 29 has been well established [1-3, 12, 62-65], one more recent interest in the electroreduction of carbonyl compounds is focused on the stereo-selective reduction of ketones. For example, the diastereo-selective cathodic coupling of aromatic ketones has been reported. In the presence of a chiral-supporting electrolyte, a low degree of enantioselectivity has been found [66] (Scheme 30). 

Asymmetric electroreduction of ketones to the corresponding chiral alcohols has recently been reported. Typical examples are the reduction of ketones bearing chiral auxiliaries [68, 69], and the indirect reduction of ketones with alcohol dehydrogenase (ADH), as a mediator (Scheme 32) [70]. 

In contrast to the high regioselectivity and good yields of electroreductive intramolecular coupling reactions of ketones with multiple bonds shown in Schemes 34 to 37, the yields of interm olecular coupling reactions have been very low until recently. However, by using carbon fiber electrodes, intermolecular coupling reactions have... 

Electroreductive coupling of ketones with silyl-substituted olefins promotes interesting reactions that are useful for organic synthesis. For example, coupKng of ketones with trimethylvinylsilanes affords /I-trimethylsilyl alcohols, which are easily transformed to the corresponding olefins (Scheme 40). This reaction is interesting from the synthetic point of view since vinylsilane behaves as the equivalent to a /I-trimethylsilyl group-substituted anion [77, 83]. 

The existence of a trimethylsilyl group on the carbon-carbon double bond seems to activate the double bond towards radical addition since the electroreductive intermolecular coupling of ketones with carbon-carbon double bond predominantly takes place at the... 

Anion radical species formed by the electroreduction of ketones also inter-molecularily add to a carbon-nitrogen double bond and form derivatives of an O -amino alcohol (Scheme 43) [85]. 

The electroreduction of disulfides R2S2 (R = Ar, Aik), in the presence of carbonyl compounds and MesSiCl, includes the formation of intermediate thiosilanes and results in trimethylsilyl ethers of hemithioacetals of ketones and aldehydes or in full thioacetals depending on whether a two-compartment (a) or an undivided (b) cell was used (Scheme 48) [218]. 

Many reductive cyclizations, including many of those that are not initiated electrochemically, correspond to variations on the electrohydrocyclization theme. The so-called electroreductive-cyclization reaction, for example, involves cyclization between the /I-carbon of an electron-deficient alkene and an aldehyde or ketone tethered to it, to form a new a-bond between these formally electron deficient centers (Scheme 2). 

Electroreduction of y- and 5-cyano ketones in isoPrOH with a Sn cathode gave a-hydroxyketones with good diastereo-selectivities as cyclization products. The reaction has been used as a key step for the synthesis of, for example, guaiazulene, triquinanes, and dihydrojasmone. Similarly, the corresponding intermolecular couplings were realized [315]. 

Reduction of nonconjugated aromatic ketones gave at metal cathodes (e.g., tin, copper, silver, palladium, zinc) the cis isomers (ds-H/OH) of cycKzed products in high diastereoselectivity. The electroreduction of 5-phenylpentan-2-one led to 70% of an exclusively ds-hexahydronaphthalene... 

The electroreductive coupling of the hindered aromatic ketones (367) has been achieved in a DMF-BU4NBr-(Hg) system by the aid of CrCh or MnCl2 as the electrocatalyst (Scheme 134) [484, 485]. The reductive coupling proceeds at a less negative potential [ 1/2 —1.44 —1.53 V (SCE)] than the reduction of the ketone (—1.63 —2.01 V). In some cases, Mn electrocatalysts favor the reduction to the carbinol (369), whereas a Cr catalyst promotes the formation of the pinacol (368). 

The mechanism of the Zn chloride-assisted, palladium-catalyzed reaction of allyl acetate (456) with carbonyl compounds (457) has been proposed [434]. The reaction involves electroreduction of a Pd(II) complex to a Pd(0) complex, oxidative addition of the allyl acetate to the Pd(0) complex, and Zn(II)/Pd(II) transmetallation leading to an allylzinc reagent, which would react with (457) to give homoallyl alcohols (458) and (459) (Scheme 157). Substituted -lactones are electrosynthesized by the Reformatsky reaction of ketones and ethyl a-bromobutyrate, using a sacrificial Zn anode in 35 92% yield [542]. The effect of cathode materials involving Zn, C, Pt, Ni, and so on, has been investigated for the electrochemical allylation of acetone [543]. 

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]. 

As noted previously, many of the cathodic cyclizations discussed in this article are variations on the electrohydrocyclization theme developed by Baizer and coworkers [8-14,16,17,21], The next section of this article, for example, deals with what has been referred to as the electroreductive cyclization (ERC) reaction, a process that leads to cycUzation between an electron-deficient alkene and an aldehyde or ketone. With this thought in mind, several of the section titles are formulated to highlight the functional groups to be joined the following is representative. 

Alternatively, CO2 can be used as source of CO. Indeed, it is well known that low-valent transition metal complexes can catalyze the chemical or electrochemical reduction of CO2 into CO. This approach was used to generate the mixed nickel complex Ni°bpy(CO)2 by the electrochemical reduction of Nibpy in NMP or DMF in the presence of CO2. The reduced complex can react with alkyl, benzyl, and allylhalides to give the symmetrical ketone along with the regeneration of Nibpy ". A two-step method alternating electroreduction and chemical coupling leading to the ketone has thus been set up (Scheme 9) [126,127]. 

Apart from the electrocarbonylation reactions of organic halides described in Sect. 6, other Ni-catalyzed reactions leading to ketones have been reported. Thus the electroreductive coupling between acylchlorides and alkyl halides, catalyzed by NiBr2bpy leads to unsymmetrical ketones [129]. Recently acylchlorides have been converted to symmetrical ketones in an undivided cell fitted with a nickel or stainless steel anode. In this reaction the active metallic species... 

A series of bicyclo[3.3.0]octanols are accessible by electroreductive tandem cyclization of linear allyl pentenyl ketones 189, as shown by Kariv-Miller et al. [189]. The electrolyses are carried out with an Hg-pool cathode and a Pt-flag anode. As electrolyte, tetrabutylammonium tetrafluororborate is used. The reaction is stereoselective, yielding only two isomers 192 and 193. In a competing reaction, a small amount of the monocyclic alcohol is formed. Since all the monocycles have the 1-allyl and the 2-methyl group in trans geometry it is assumed that this terminates the reaction. The formation of a bicyclic product requires that the first cyclization provides the cis radical anion which leads to cis-ring juncture [190] (Scheme 37). 

The electroreductive cyclization of ketones and aldehydes linked to cc,P-unsaturated esters 205 has been investigated by Little and co-workers. Good... 

Shono and Kise have investigated the electroreductive coupling reaction of y- and -cyanoketones, yielding bicyclic a-hydroxy ketones 218 and their dehyd-roxylated equivalents 221 [198], Optimized yields are obtained when the electroreduction is carried out in i-propanol at a controlled potential of — 2.8 V using a divided cell equipped with a ceramic diaphragm and an Sn or Ag cathode. The product ratio is controlled by the reaction temperature. When the reaction is carried out at 25°C, almost exclusively the a-hydroxy ketone 218 is obtained, whereas at 65°C the obviously thermally dehydroxylated ketone 221 is the predominant product (Scheme 42). Furthermore, this methodology has been... 

For the reduction of aliphatic ketones to hydrocarbons several methods are available reduction with triethylsilane and boron trifluoride [772], Clemmensen reduction [160, 758] (p. 28), Wolff-Kizhner reduction [280, 281, 759] (p. 34), reduction of p-toluenesulfonylhydrazones with sodium borohydride [785], sodium cyanoborohydride [57i] or borane [786] (p. 134), desulfurization of dithioketals (jaeicaipioles) [799,823] (pp. 130,131) and electroreduction [824]. 

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