Aldehydes electroreduction

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). 

Reisse used activated zinc for aqueous Barbier-type reactions.66 Submicromic zinc powder produced by pulsed sono-electroreduction is about three times more effective than the commercial variety. The stereochemical course of the allylation and propargylation of several aldehydes with crotyl and propenyl halides using zinc powder as the... 

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

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 aromatic esters to the corresponding aldehydes is accomplished by the reduction of esters in the presence of chlorotrimethylsilane (CTMS) (Scheme 14) [31]. 

Appropriate activation of carboxyl groups enables reduction of aliphatic carboxylic acids to the corresponding aldehydes. The electroreduction of iminium salts prepared from aliphatic carboxyKc... 

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... 

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). 

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. 

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

Thioamides were converted to aldehydes by cautious desulfurization with Raney nickel [1137, 1138] or by treatment with iron and acetic acid [172]. More intensive desulfurization with Raney nickel [1139], electroreduction [172], and reduction with lithium aluminum hydride [1138], with sodium borohydride [1140] or with sodium cyanoborohydride [1140] gave amines in good to excellent yields. 

TABLE 1. Electroreductive coupling between CF3Br and aldehydes... 

Little s group has reported electroreductive cyclizations involving ,/l-unsaturated esters (equation 34)96. Based upon CV measurements, the conjugated ester rather than the aldehyde or ketone is suggested to be the electron acceptor. Although direct cyclization of... 

The formation of the y-lactams is almost perfectly diastereoselective if cyclic a-amino aldehydes or the aldehyde prepared from valine are used as starting materials. As it is shown in the following scheme, the electroreduction of the obtained optically pure y-lactams followed by the reduction with LAH yields the corresponding optically pure pyrrolizidine and indolizidine skeletons. 

Symmetrical ketones are also prepared from organic halides and carbon dioxide catalyzed by 2,2 -bipyridine-nickel complexes42. Torii and coworkers found a synthetically useful electrochemical allylation, which involves the electroreductive generation of a dial-lyltin reagent in the presence of a catalytic amount of tin. A wide variety of aldehydes and ketones have been added in high yields under relatively mild conditions by this method (equation 19)43. The process was further improved by the addition of catalytic amounts of... 

Fig. 22 Electroreduction of ketones or aldehydes using ADH as catalyst. Reduction system A shows the ADH-catalyzed reduction coupled with regeneration of NADPH or NADH by ferre-doxin-NADP+ reductase (FNR) or diaphorase (DP), respectively with assistance of methyl violo-gen as an electron mediator. In system B, ADH is used as sole enzyme which catalyzes both reduction of substrates and regeneration of cofactors...

The effective electroreductive pinacolization has been exemplified in the terpene series, i.e. aldehydes such as retinal and ketones such as a- or j8-ionone give the corresponding pinacols in good yields when electrolyzed in a DMF-sodium per-chlorate-Hg system or with a Pt cathode in the presence of tin [8, 9]. 

The utility of electroreductive cyclization (ERC) reaction is demonstrated by the formal total synthesis of the antitumor agent quadrone (120) that is outlined in Scheme 13 [35]. The reaction serves to link the -carbon of an electron deficient alkene to the carbonyl carbon of an aldehyde or ketone tethered to it. The transformation plays a pivotal role in the key carbon-carbon bond forming events leading to 124 and 122, and en route to quadrone (120). 

An interesting and useful variation on the electroreductive cyclization theme calls for the use of substrates wherein an allene or alkyne is tethered to an aldehyde or ketone [38]. As exemplified by the conversion of 139 or 143 to 141, the reductive cyclizations lead to an allylic alcohol. This functionality, of course, is exceptionally useful, offering the opportunity for a host of followup reactions to be employed. 

The most systematically investigated acyl anion equivalents have been the IMS ethers of aromatic and heteroaromatic aldehyde cyanohydrins, TBDMS-protected cyanohydrins, - benzoyl-protected cyanohydrins, alkoxycaibonyl-protected cyanohydrins, THP-protected cyanohydrins, ethoxyethyl-protect cyanohydrins, a-(dialkylamino)nitriles, cyanophosphates, diethyl l-(trimethylsiloxy)-phenyimethyl phosphonate and dithioacetals. Deprotonation di these masked acyl anions under the action of strong basie, usually LDA, followed by treatment with a wide varies of electrophiles is of great synthetic value. If the electrophUe is another aldehyde, a-hydroxy ketones or benzoins are formed. More recently, the acyl caibanion equivalents formed by electroreduction of oxazolium salts were found to be useful for the formation of ketones, aldehydes or a-hydroxy ketones (Scheme 4). a-Methoxyvinyl-lithium also can act as an acyl anion equivalent and can be used for the formation of a-hydroxy ketones, a-diketones, ketones, y-diketones and silyl ketones. - - ... 

---