Single Electron Transfer Reductions

In addition to ring opening, the reaction of sodium with the oxabicyclic substrate 236 resulted in elimination of methoxymethoxide and reduction of the diene [118]. Only one olefinic product 237 was isolated, Eq. 144. 

William s synthesis of a model compound of the dolastanes employed sodium naphthalide to induce the ring opening of the allylic ether, Eq. 146 [59]. Protonation at the y carbon gave the conjugated enone. 

The samarium iodide promoted reduction of substrate 242 also led to ring opening to yield hydroxycyclohexenone 243 in De Clercq s synthesis of a precursor to the A-ring of 1 a-hydroxyvitamin D3, Eq. 148 [196]. 

In Vogel s studies, the [2.2.1] oxabicydic substrate 244 was found to undergo reductive ring opening as well as thermodynamic protonation to furnish a cyclohexanol, Eq. 149 [197]. 

Enantiomerically enriched substrate 245 was found to undergo reductive ring-opening in the presence of Sml2 however, much more efficient opening was observed using lithium in ammonia, Eq. 150 [120]. 

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Robinson, J. M., Flynn, E. T., McMahan, T. L., Simpson, S. L., Trisler, J. C., Conn, K. B. Benzoin enediol dianion and hydroxide ion in DMSO a single electron transfer reduction system driven by the irreversible benzilic acid rearrangement. J. Org. Chem. 1991, 56, 6709-6712. 

In an attempt to elucidate the structure of the diterpene marrubiin, a lithium/ammonia reduction on dchydrotetrahydromarrubic acid was carried out stereoselectively, giving the axial alcohol10. This example along with those of 12-oxosteroids (see p 3974) represent reasonably well-documented exceptions to equatorioselectivity in single electron transfer reductions of cyclohexanones. 

In the case of a 17-oxosteroid, 3-methoxy-14a-melhylestra-l,3.5(10)-trien-17-one. reduction with sodium/2-propanol provided the 17-alcohols in 84 6 ratio (/ /a)19. MMX calculations19 suggest a ratio of 85 15 (/ / ) at equilibrium. Thus, the single electron transfer reduction provided the more stable cyclopentanol. 

Lithium/ammonia reduction was also utilized in a multistep synthesis of a 4-norsteroid starting from 2,3,7,7a-tetrahydro-l//-indene-l,5(67/)-one40. In this case the introduced acetal protecting group is inert in the single electron transfer reduction. 

The mechanism by which the Birch reduction of benzene takes place (Figure 118) IS analogous to the mechanism for the metal-ammonia reduction of alkynes It involves a sequence of four steps m which steps 1 and 3 are single electron transfers from the metal and steps 2 and 4 are proton transfers from the alcohol... 

When equimolar quantities of 80a and its dication 110 are combined in acetonitrile, single electron transfer occurs and the coproportionation product was obtained (95TL2741).Tliis deeply red-colored, air-sensitive radical cation 111 showed a strong ESR signal (g = 2.0034). On the other hand, the excellent electron donor 80a could be prepared by electrolytic reduction starting from 110. It was necessary to carry out the reduction with scrupulous exclusion of oxygen. Tlius, the electrolysis of 110 at -1.10 V initially gave rise to an intense red color, which was presumably due to the formation of 111. Upon further reduction, the red color faded and the tetraaza-fulvalene 80a was isolated at a 62% yield (Scheme 45). 

The complex cyanides of transition metals, especially the iron group, are very stable in aqueous solution. Their high co-ordination numbers mean the metal core of the complex is effectively shielded, and the metal-cyanide bonds, which share electrons with unfilled inner orbitals of the metal, may have a much more covalent character. Single electron transfer to the ferri-cyanide ion as a whole is easy (reducing it to ferrocyanide, with no alteration of co-ordination), but further reduction does not occur. 

B. Reductions by Hydrides, Metals and Single-Electron-Transfer (SET)... 

Fig. 8 Reactions of various carbocations with Kuhn s anion [2 ] as compared with their reduction potentials (peak potentials measured vs. Ag/Ag in acetonitrile by cyclic voltammetry cf. Tables 1 and 8 and Okamoto et al., 1983). SALT, salt formation COV, covalent bond formation ET, single-electron transfer. 

As the cation becomes progressively more reluctant to be reduced than [53 ], covalent bond formation is observed instead of electron transfer. Further stabilization of the cation causes formation of an ionic bond, i.e. salt formation. Thus, the course of the reaction is controlled by the electron affinity of the carbocation. However, the change from single-electron transfer to salt formation is not straightforward. As has been discussed in previous sections, steric effects are another important factor in controlling the formation of hydrocarbon salts. The significant difference in the reduction potential at which a covalent bond is switched to an ionic one -around -0.8 V for tropylium ion series and —1.6 V in the case of l-aryl-2,3-dicyclopropylcyclopropenylium ion series - may be attributed to steric factors. 

Although single-electron-transfer (SET) processes would be expected to be important in reactions that use metals as reagents, this type of process has also been recognized in the reduction of carbonyl groups that involve 1,4-dihydronicotinamide derivatives . Recent work by Oae and coworkers" has shown that an SET process is operative in the reduction of dibenzothiophene S-oxide by l-benzyl-l,4-dihydronicotinamide when the reaction is catalyzed by metalloporphins. The reaction is outlined in equation (18), but the study gave results of much more mechanistic than synthetic value. This type of study is relevant to understanding biochemical mechanisms since it is known that methionine sulphoxide is reduced to methionine by NADPH when the reaction is catalyzed by an enzyme isolated from certain yeasts . 

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. 

Anti stereospecificity is associated with a concerted reductive elimination, whereas single-electron transfer fragmentation leads to loss of stereospecificity and formation of the more stable A-stereoisomer. 

The values of E° for Eqs. (15)-(20) indicate that if multielectron reductions of C02 take place, for example, by using suitable catalysts, the potentials required are much less negative than that for single-electron transfer, C02/C0J, and are also less negative... 

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