Diimide, reduction

Chlorins, e.g. 14, form adducts with osmium(VIII) oxide, which can be hydrolyzed in aqueous sodium sulfide to bacteriochlorindiols, e g. 2, or isobacteriochlorindiols, e.g. 3. Thus, similar to diimide reductions of chlorins, metal-free tetraphenylchlorin 14 (M = 2H) is selectively oxidized to a corresponding bacteriochlorin 2 whereas the zinc chlorin gives an isobac-teriochlorin 3 on oxidation with osmium(VIII) oxide.40 With less symmetrical chlorins, very complex mixtures of constitutional isomers and stereoisomers are formed by /i-bishydroxyla-tion.17... 

The diimide reduction of nietal-free 5,10,15,20-tetraphenylporphyrin (2) or 5,10,15,20-tetraphenyl-2,3-dihydroxychlorin (3) gives the bacteriochlorins 1 in good yields. 

Isobacteriochlorins, since they are tetrahydroporphyrins, can be obtained by tetrahydrogena-tion of porphyrins and dihydrogenation of chlorins. However, alkali-metal reduction of porphyrins and metalloporphyrins always gives a mixture of chlorins, bacteriochlorins or isobacteriochlorins.14 The method of choice for the preparation of pure isobacteriochlorins, e.g. 2, is the diimide reduction of zinc(II) chlorins, e.g. l.15a,b... 

The addition is therefore stereospecifically syn and, like catalytic hydrogenation, generally takes place from the less-hindered side of a double bond, though not much discrimination in this respect is observed where the difference in hulk effects is small.Diimide reductions are most successful with symmetrical multiple bonds (C=C, C=C, N=N) and are not useful for those inherently polar (C=N, C=N, C=0, etc.). Diimide is not stable enough for isolation at ordinary temperatures, though it has been prepared as a yellow solid at — 196°C. 

Since the corresponding endoperoxide precursors are all too unstable for isolation, the diimide reduction constitutes an important chemical structure confirmation of these elusive intermediates that are obtained in the singlet oxygenation of the respective 1,3-dienes. However, the aza-derivative 14 and the keto-derivative 15 could not be prepared,17> because the respective endoperoxides of the pyrroles 18) and cyclopentadienones suffered complex transformations even at —50 °C, so that the trapping by the diimide reagent was ineffective. 

The bicyclic peroxide 11 was prepared via diimide reduction of the endoperoxide derived from spirocyclopentadiene (Eq. 8)21>. As before, at elevated temperature the labile endoperoxide rearranges into diepoxide and ketoepoxide,22) but diimide reduction at —78 °C allows trapping leading to the highly strained bicyclic peroxide 11. 

A number of the bicyclic ozonides 12 were prepared in good yield (45-65 %) by diimide reduction of furan singlet oxygenates (Eq. 9) 23>. Again, low temperature were essential because the furan endoperoxides readily transform into 1,2-diacyl-ethylenes. Of course, the bicyclic ozonides 12 can alternatively be prepared via ozonolysis of the appropriate 1,2-disubstituted cyclobutene 24). 

On the other hand, the thiaozonides 13 were unknown but could be prepared analogously via singlet oxygenation of 2,5-disubstituted thiophenes and subsequent diimide reduction at low temperature (Eq. 10)25). 

In addition to the parent compound 2, the derivatives 2a, b, the benzo-system 16, the lactone-peroxides 17, and the fused polycyclic derivatives 18 and 19 could be prepared via the singlet oxygen-diimide route. For example, the parent system 2 was obtained in ca. 40% yield by diimide reduction of the stable 1,3-cyclohexadiene endoperoxide in MeOH at 0 °C27,28). Dihydroascaridole 2a and dihydroergosterol endoperoxide... 

The benzo-derivative 16 is accessible through 1,4-dimethylnaphthalene, which on singlet oxygenation leads to the thermally labile naphthalene-1,4-endoperoxide. This endoperoxide expels singlet oxygen at ca. 10 °C, but diimide reduction below 0 °C in MeOH affords the stable dihydro derivative 16 (Eq. 11). 

The lactone-peroxides 17 are derived from the corresponding ot-pyrones. Singlet oxygenation at low temperature affords the unstable a-pyrone endoperoxides which, on warming up, readily decarboxylate into 1,2-diacylethylenes. However, subambient diimide reduction leads to the desired lactone peroxides 17 (Eq. 12)29). 

Similarly, the cyclobutane-fused bicyclic peroxide 19 was prepared by diimide reduction of the corresponding bicyclic endoperoxide derived from 1,3,5-cyclooctatriene (Eq. 14)31a). 

Alternatively, the (2 + 4)-tropilidene endoperoxide, which is the major product in the singlet oxygenation of cycloheptatriene 30 a) affords on diimide reduction the desired bicyclic peroxide 20. The double bond in the two-carbon bridge is reduced selectively, but on exhaustive treatment with excess diimide, the fully saturated substance is obtained. A number of substituted derivatives have been prepared in this way30). 

The keto-derivative 21 is of interest because the relatively unreactive 3,5-cyclo-heptadienone substrate, which towards most dienophiles reacts with double bond isomerization, affords the desired endoperoxide (Eq. 16)33). Diimide reduction proceeds smoothly, leading to the keto-peroxide 21 in over 90% yield. 

The strained dienic endoperoxide is readily reduced by diimide, leading to the relatively stable bicyclic peroxide in high yield. Again, aprotic solvents such as CH2C12 or CFClj are essential for the diimide reduction, because in MeOH complex rearrangements take place 30d e>. 

The diimide reduction again proceeds sluggishly and several recycles are essential to achieve complete conversion. The doubly unsaturated endoperoxide is the major product in the singlet oxygenation of 1,3,5-cyclooctatriene (Eq. 14). 

Use of mild conditions was crucial and the development of diimide reduction of singlet oxygenates, silver-salt-assisted displacement of halide by peroxide nucleophiles, peroxymercuration and demercuration, peroxide transfer from organotin to alkyl triflates, and oxygen trapping of azoalkane-derived diradicals have all played a part in providing the rich harvest of new bicyclic peroxides described herein. 

In general, trans double bonds are more reactive than cis double bonds, and diimide reduction is not accompanied by migration or by cis-trans isomerization of the double bonds (equation 24)77. 

The origin of stereofacial selectivity in electrophilic additions to methylene-cyclohexanes (2) and 5-methylene-l,3-dioxane (3) has been elucidated experimentally (Table 2) and theoretically. Ab initio calculations suggest that two electronic factors contribute to the experimentally observed axial stereoselectivity for polarizable electrophiles (in epoxidation and diimide reduction) the spatial anisotropy of the HOMO (common to both molecules) and the anisotropy in the electrostatic potential field (in the case of methylenedioxane). The anisotropy of the HOMO arises from the important topological difference between the contributions made to the HOMO by the periplanar p C-H a-bonds and opposing p C—O or C—C cr-bonds. In contrast, catalytic reduction proceeds with equatorial face selectivity for both the cyclohexane and the dioxane systems and appears to be governed largely by steric effects. ... 

The relative reactivities toward diimide cover a range of -10, from 1,2-dimethylcyclohexene to norbornene (ref. 6). Electron attractive substituents increase the reactivity of the double bond towards diimide although the data to place compounds such as maleic acid or acrylonitrile on the scale for Garbisch s hydrocarbons is lacking (ref. 21b). Garbisch et al. found that the main factors that contribute to the observed reactivities in diimide reductions of unsaturated hydrocarbons, eqn. (3), are torsional strain, bond angle... 

The correlation between the apparent association constants, K. which are derived from the competitive rates on Pt and reductions by diimide indicates that structural changes in the alkene generally have parallel effects on these reactions, Fig. 2. Because the diimide reduction is essentially free of steric effects, this effect is liable to account for some of the differences which are observed in extended groups of compounds. The small range of individual reactivities on Pt, which are zero order in alkene, can be understood in that the variation in structure which increases the driving force towards... 

Effect of structure of cycloalkenes on the individual rates of hydrogenation (relative to cyclopentene) on metal catalysts compared to diimide reductions. 

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