Alkenic electroreduction

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... 

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). 

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. 

Electroreductive Cyclization Electron Deficient Alkene/Carbonyl... 

Esters are difficult to reduce, and are inert to many of the conditions used in electroreductive processes. A recent investigation has demonstrated that they can easily be reduced at a magnesium cathode in the presence of t-BuOH [52,53]. When tethered to an alkene, cyclization occurs to afford a cyclic alcohol. Two examples are illustrated, the second being a key step in a synthesis of racemic muscone [53]. 

Little has investigated monoactivated and doubly activated alkenes tethered to butenolide with respect to electroreductive cyclization [202]. The geminally activated systems 227 undergo cyclization to diastereomeric products 228 and 229 in an 1 1 mixture, whereas both the a,j8-unsaturated monoester and a,/ -unsaturated mononitrile fail to cyclize. Only saturation of the C-C double bond of butenolide is observed. The author explains these results by distinct reactivity and lifetime of the intermediate radical anions. The radical anions derived from the monoactivated olefins are less delocalized than those of 227 and therefore should be shorter lived and more reactive. In this case preferential saturation occurs. The radical anions derived from the doubly activated alkene 227 are comparatively long-lived and less basic and thus capable of attacking the C-C double bond of the butenolide moiety. A decrease in saturation, accompanied by a marked increase in cyclization, is observed. 

Triple bonds in side chains of aromatics can be reduced to double bonds or completely saturated. The outcome of such reductions depends on the structure of the acetylene and on the method of reduction. If the triple bond is not conjugated with the benzene ring it can be handled in the same way as in aliphatic acetylenes. In addition, electrochemical reduction in a solution of lithium chloride in methylamine has been used for partial reduction to alkenes trans isomers, where applicable) in 40-51% yields (with 2,5-dihydroaromatic alkenes as by-products) [379]. Aromatic acetylenes with triple bonds conjugated with benzene rings can be hydrogenated over Raney nickel to cis olefins [356], or to alkyl aromatics over rhenium sulfide catalyst [54]. Electroreduction in methylamine containing lithium chloride gives 80% yields of alkyl aromatics [379]. 

Most of the current preparative methods of oximes from nitroalkenes are not versatile. Reduction of nitroalkenes by CrCl2 or NaH2P02 in the presence of palladium was reported to afford the corresponding oximes, but the yields are not satisfactory. Zn-acetic acid and Na2Sn02 reductions are limited to the preparation of ketoximes only. Electroreduction of alkenes was reported to yield mixmres of ketones and ketoximes, or oximes and acetals (or ketones) depending on the strucmre of nitroalkanes. 

Sera and coworkers, during their investigation on electroreduction of nitroalkenes, found that plates of powder or metalhc lead can reduce nitroalkene 20 to give oxime 21 in acetic acid-DMF solution without electricity (Scheme 18). The reduction of 1-nitro-1-alkenes afforded the corresponding aldoximes or ketoximes in excellent yield. 

Organic electroreductions at mercury cathodes in tetraalkylammonium (TAA+) electrolyte solutions at the limit of the cathodic potential window are described. Aromatic hydrocarbons, fluorides, ethers and heterocycles, as well as aliphatic ketones, alkenes and alkynes have been studied, using both aqueous and non-aqueous solvents. At these very negative potentials neither the TAA+ cation nor the mercury cathode are inert, instead they combine to form TAA-mercury. It is hypothesized, and supporting evidence is presented, that TAA-mercury serve as mediators in the organic electroreductions. The mediated reactions show remarkable selectivity in certain cases and it is shown that this selectivity can be improved by the choice of the TAA +. 

Electroreduction of triphenylphosphino- or 1,2-bisdiphenylphosphinoethanenickel(II) complexes in ethanol via zero valent complexes with halobenzenes has been described87. Arylation of olefins (equation 55) can be achieved by electro generated Ni(0) complex 106, associated with triphenylphosphine and an alkene (107). The optimum conditions for the reaction include the use of one to three equivalents of triphenylphosphine and a base such as triethylamine30. 

Conjugation between the triple bond and the carbonyl function lowers the reduction potential considerably whereas alkyl substitution makes reduction more difficult (entries 1-5). A comparison between the half-wave potentials for reduction of PhC=CPh (1-69 V, vs. Hg pool) and // <7/t -PhCH=CHPh (1-65 V) substantiates the fact that, at least for this case, a likely product of reduction is more vulnerable to electroreduction than the starting material. In practice electrolyses in protic media aimed at producing alkene from alkyne usually proceed to give alkane. 

Kariv-Miller and coworkers have developed indirect electroreductive cyclizations with the dimethyl-pyrrolidinium ion (DMP") as a mediator. Preparative electrolysis of 6-hepten-2-one (9) at a graphite cathode afforded cu-dimethylcyclopentanol (10) in 90% yield (equation 5). The reduction is believed to occur via the ketyl radical anion, which cyclizes onto the alkenic bond. In the absence of DMP simple reduction to 6-hepten-2-ol takes place.Very recently it was shown that instead of DMP several aromatic hydrocarbons can be used as mediators to initiate the cyclization reaction. The carbonyl group can also be cyclized onto an alkynic bond and even an aromatic ring. - ... 

When an alkenic bond is conjugated with the carbonyl group, the carbonyl carbon and the p-carbon become the two reactive centers and a variety of products can be obtained depending on the medium. Presence of water in the reduction of 4-methyl-2-cyclohexenones results in a mixture of products. However, when the p-position is substituted such as in retinal (11), pinacolization takes place to form the pinacol (12) in 89% yield, provided that the electroreduction is carried out in an aprotic medium in the presence of a mild proton donor, such as diethyl malonate (equation 6). ... 

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). 

The electroreduction of alkenes activated by electron-withdrawing substituents, at a compact sulfur/carbon cathode in aprotic media affords thioorganic compounds.23 The electrode is prepared by melting a mixture of sulfur and graphite and serves as a source of nucleophilic polysulfides. 

The tributyltin hydride-mediated carbon-carbon bond formation via radical addition and cyclization of alkyl halides with alkenes has often been a choice for construction of various organic molecules [1], However, the requirement for high-temperature initiators or photo initiation and the difficulties associated with purification of the products from tributyltin halides tend to limit the widespread use of these methods, despite the efforts to make the methods easier [Ic, 2], Recently, nickel-mediated radical additions and cyclizations have been introduced as promising alternatives to the tributyltin hydride methods. These are the nickel powder-acetic acid method for cyclization of haloamides to y-lactams, y -lactams and in-dolones, the borohydride exchange resin-nickel boride method for radical addition, nickel-catalyzed electroreductive cyclization and nickel-catalyzed Kharasch addition of polyhalo compounds. 

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