Electron transfer reduction enones

Reduction of Ketones and Enones. Although the method has been supplanted for synthetic purposes by hydride donors, the reduction of ketones to alcohols in ammonia or alcohols provides mechanistic insight into dissolving-metal reductions. The outcome of the reaction of ketones with metal reductants is determined by the fate of the initial ketyl radical formed by a single-electron transfer. The radical intermediate, depending on its structure and the reaction medium, may be protonated, disproportionate, or dimerize.209 In hydroxylic solvents such as liquid ammonia or in the presence of an alcohol, the protonation process dominates over dimerization. Net reduction can also occur by a disproportionation process. As is discussed in Section 5.6.3, dimerization can become the dominant process under conditions in which protonation does not occur rapidly. 

Recently it has been shown that radical anionic cyclization of olefinic enones effectively compete with intramolecular [2 -I- 2]-cycloaddition to form spirocy-clic compounds [205, 206], 3-Alkenyloxy- and 3-alkenyl-2-cyclohexenones 235 are irradiated in the presence of triethylamine. As depicted in Scheme 46 two reaction pathways may operate. Both involve electron transfer steps, either to the starting material (resulting in a direct cyclization) or to the preformed cyclobutane derivative 239, which undergoes reductive cleavage. The second... 

Mechanistic studies are consistent with photochemical electron transfer from the carbyne complex to chloroform followed by H atom abstraction. Ring expansion then occurs to give a metallacyclopentene, which undergoes carbonyl insertion. Finally, reductive elimination yields the cyclopentenone complex that slowly releases the free enone (equation 119)158. 

Tertiary amines have also been employed in electron transfer reactions with a variety of different acceptors, including enones, aromatic hydrocarbons, cyanoaro-matics, and stilbene derivatives. These reactions also provide convincing evidence for the intermediacy of aminoalkyl radicals. For example, the photoinduced electron transfer reactions of aromatic hydrocarbons, viz. naphthalene, with tertiary amines result in the reduction of the hydrocarbon as well as reductive coupling [183, 184]. Vinyl-dialkylamines can be envisaged as the complementary dehydrogenation products their formation was confirmed by CIDNP experiments [185]. 

One can ascribe the stereo specificity of this reduction to the tripartite transition state shown opposite. In this mechanistic proposal,5 two very rapid and successive single-electron transfers occur from the Cr(II) reagent to opposite sides of the triple bond. This leads to a vinyl-dichromium species 22 that subsequently protonates with retention of configuration to produce the trans-enone 23 (Scheme 7.6). 

The irradiation of enone 20 in the presence of Et3N or DABCO as electron donors yields 21 as major product and almost none of the valence tautomerized product 22 (equation 29)139. Photomediated electron transfer apparently differs here from alternative electron transfer processes, since in lithium/liquid ammonia and electrochemical reductions 22 is produced. 

Raney niekel can be used for the ehemoselective reduction of a,y9-unsaturated ketones, esters, acids, nitriles, and nitroalkenes to give the corresponding saturated carbonyl compounds and carbonyl analogs in excellent yields. From trapping experiments it became evident that electron transfer from nickel to give the enone radical anion initiates the reaction which then proceeds via proton transfer and second electron-proton transfer cycle (Scheme 8) [37]. 

A number of studies have been made of the reduction of model enones in buffered aqueous or buffered ethanolic solutions in order to elucidate the sequence of electron transfer, proton transfer, and coupling steps as a function of pH [39-42,91-95]. The experimental methods applied include polarography, CV, LSV, and chronocoulometry. 

The Sn2 mechanism is ruled out for reaction between the tertiary halide, r-BuBr, and radical anions derived from the more easialy reduced compounds cinnamonitrile (9) ethyl cinnamate (12a), methyl styryl ketone (23a), and phenyl styryl ketone (20a). Reduction of the activated alkenes in the presence of an excess of r-BuBr leads to mixtures of products where a r-Bu group has been introduced in a- or j0-position or in the phenyl ring. For 9 and 12a small amounts of butylated hydrodimers were obtained in addition, and for the enone 23a formation of the unsaturated alcohol with introduction of the /-Bu group at C-1 was a major product [192]. In this case the mechanism is unambiguously reduction of the activated alkene followed by electron transfer to r-BuBr concerted with halide cleavage, in... 

An interesting observation from organocuprate chemistry is that the initial step in 1,4-addition to enones may be electron transfer. Thus the relative reactivity of enones toward conjugate addition parallels their ease of reduction. One problem with any reaction between a ketone or aldehyde and a metal alkyl is deprotonation, when a hydrogens are present, to yield an enolate. Given the considerable basicity of metal alkyls, this side reaction should be anticipated. 

Chromium(II) chloride reduction of 9a-bromo-A -3-oxosteroids 19 leads to 5,9-cyclosteroids 20. The formation of these eyclosteroids is explained by assuming a one-electron transfer in the cleavage of the C-Hal bond with chromium(II) chloride to give a carbon radical, followed by a second one-electron transfer from Cr to give a carbanionic intermediate that intra-molecularly undergoes addition to the enone moiety and thus forms the cyclopropane ring. 

Cyclopentanols (134) are formed by the photo-reductive cyclization of the enones (135). Reactions are carried out in HMPA and irradiation of the enones (135) in this medium effects electron transfer to yield the radical anion of the carbonyl group. Cyclization follows the "Rule of Five" and yields the cyclopentanols. ... 

Reductive dimerization of chalcones by ultrasonically dispersed potassium (UDP) is initiated by an electron transfer to the enone system. The reaction is not selective however, details are not easily available. ... 

A mechanism suggested by House and Umen (1972, 1973) is outlined in Scheme 13. The essential process is an initial electron transfer from the cuprate to the enone. Polarographic reduction potentials of the enones... 

The mechanism of action of the nickel addend proceeds probably through a reduced form of nickel (e.g. nickel(I)) which is involved in a electron transfer process with the enone. Further reaction with the organozirconium reagent affords the addition product through transfer of the organic radical from zirconium to the nickel center, followed by a reductive elimination step (see [45] for a similar mechanistic proposal). 

The reduction of enones by electron transfer has been studied further, a comparison being drawn between ammonia and hexamethylphosphoramide as solvents. In general, reduction with sodium in hexamethylphosphoramide yields more of the less stable saturated ketone epimer than is observed in ammonia methods of optimizing this selectivity are discussed. ... 

Mattay, J., Banning, A, Bischof, E.W., Heidbreder, A., and Runsink, J., Radical ions and photochemical charge transfer phenomena. 36. Photoreactions of enones with amines. Cyclization of unsaturated enones and reductive ring opening by photoinduced electron transfer (PET), Chem. Ber., 125,2119,1992. 

The normal Birch reduction is most interesting when applied to aromatic ethers 209 or acids 213. The addition of two electrons may make a dianion in which the charges keep away from the ether 210 but conjugate with the acid 214. Protonation of 210 gives the enol ether 211 and hence the non-conjugated enone 212. The dianion 214 has a proton which transfers to the less stable anion leaving the enolate 215 that can be alkylated to give 216. None of these compounds is chiral and there appears to be little scope for asymmetric induction. 

A great variety of substituted enolates can be obtained by the addition of nucleophiles (XeMe) to enones (for X = trialkylsilyl, see Section D.4.3.). Reductive formation of these enolates (where X = hydrogen), however, can be achieved either by hydride transfer or by a two-electron reduction combined with proton abstraction from a suitable partner. Consecutive protonation produces the diastereomeric ketones. 

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