Hydroperoxides reduction

Applications of peroxide formation are underrepresented in chiral synthetic chemistry, most likely owing to the limited stability of such intermediates. Lipoxygenases, as prototype biocatalysts for such reactions, display rather limited substrate specificity. However, interesting functionalizations at allylic positions of unsaturated fatty acids can be realized in high regio- and stereoselectivity, when the enzymatic oxidation is coupled to a chemical or enzymatic reduction process. While early work focused on derivatives of arachidonic acid chemical modifications to the carboxylate moiety are possible, provided that a sufficiently hydrophilic functionality remained. By means of this strategy, chiral diendiols are accessible after hydroperoxide reduction (Scheme 9.12) [103,104]. 

Extensive studies have established that the catalytic cycle for the reduction of hydroperoxides by horseradish peroxidase is the one depicted in Figure 6 (38). The resting enzyme interacts with the peroxide to form an enzyme-substrate complex that decomposes to alcohol and an iron-oxo complex that is two oxidizing equivalents above the resting state of the enzyme. For catalytic turnover to occur the iron-oxo complex must be reduced. The two electrons are furnished by reducing substrates either by electron transfer from substrate to enzyme or by oxygen transfer from enzyme to substrate. Substrate oxidation by the iron-oxo complex supports continuous hydroperoxide reduction. When either reducing substrate or hydroperoxide is exhausted, the catalytic cycle stops. 

Regioselective [4-1-2] cycloadditions to Cjq are also possible with 2,3-dimethyl-buta-1,3-diene (4) and with the monoterpene 7-methyl-3-methylideneocta-l,6-diene (5, myrcene) [22]. These monoadduct formations proceed under mild and controlled conditions. Most of these addition products of 1,3-butadiene derivatives (e.g. 4, 5, 8-12) are unstable against air and light [25]. The dihydrofuUerene moiety in the Diels-Alder adducts act as a 02-sensitizer and promotes the oxidation of the cyclohexene moiety to the hydroperoxide. Reduction of the hydroperoxide with PPhj yields the corresponding allylic alcohols [25]. 

The sulfur oxidation is carried out at pressure higher than 8 atm and below 180 °C, with a proprietary supported-Mo oxide-based catalyst, for example, an alpha alumina-supported MgMo04 catalyst, operating at 110 °C and 17 atm [59c]. All the products produced by oxidation side reactions and by hydroperoxide reduction are separated from the gas oil stream together with the sulfones. This operation may result in diesel yield loss therefore, the valorization or upgrade of this oxidized stream affects the process economics. This stream can be blended into the heating oil pool or treated in a hydrocracking unit to recover valuable products. 

Metallation of a-substituted a,P-unsaturated nitriles followed by introduction of dry oxygen gas results in the regioselective trapping of the delocalized anion at the a carbon to produce the hydroperoxide. Reduction with aqueous NujSO, and exposure of the cyanohydrin to NaOH affords the p.y-unsaturated ketones in good yields (Scheme 6.57).- 5 ... 

For each solvent, aldehyde and hydroperoxide reductions via the A-26, IRA-400, XE-279, and IRA-458 borohydride-form resins were investigated. Amorphous sodium borohydride and tetraethylammonium borohydride were used for comparison. Studies were run at both ambient temperature and at 45°C. Percent hydride of each resin was determined immediately prior to use. 

Hydroperoxide Reduction. The results of the cumene hydroperoxide reductions are shown in Table II. These results differ significantly from the aldehyde reduction studies. 

Based on the stability and aldehyde and hydroperoxide reduction studies, the macroreticular borohydride-form styrene-DVB resin (A-26) appears to be the most reactive reducing agent of those investigated. This polymer-bound borohydride reagent was thus selected for investigation of several application areas of interest. 

Since singlet oxygen is a dienophile, such oxidations are believed to involve cycloaddition of oxygen to an endoperoxide (46, Scheme 14), followed by rearrangement to the hydroperoxide. Reduction in steric strain and the formation of a strong intramolecular hydrogen bond (vmax 2800 cm 1) could provide the driving force in the second step.48... 

It is obvious from Table 1 that the material balance for CHP is excellent. CHP is essentially quantitatively accounted for as cumyl alcohol and acetophenone. These results agree well with those from previous studies of hydroperoxide reduction by amines (2) alcohols are usually obtained in greater than 80% yield. Alkoxy radical products are also formed, consistent with our observation of acetophenone from /3-scission of the cumyloxy radical. 

Linalool can be obtained from pinene extracts by hydrogenation, subsequent oxidation to the respective hydroperoxides, reduction to the respective alcohols and pyrolysis to linalool (Fig. 16.9). Pinene extracts mostly contain mixtures of a- and yS-pinene. After hydrogenation a mixture of cis- and trans-pinane is obtained. 

The phosphite efficiency in hydroperoxide reduction decreases in the order phosphites > alkyl phosphites > aryl phosphites > hindered aryl phosphites. Hindered aryl phosphites can also act as chain breaking primary antioxidants when substituted by alkoxy radicals but their activity is lower than that of hindered phenols but in oxidizing media at high temperatures the hydrolysis of aryl phosph(on)ites takes place and produces hydrogen phosph(on)ites and phenols which are effective chain-breaking antioxidants. Multifunctional stabilizers such as those containing HAS-phosph(on)ites moieties show a superior efficiency due to the intramolecular synergism—Table 6 [49]. 

Fig. 5 Representative electrocatalytic voltammograms of c) t P450 2E1 films assembled with polyions on pyrol3dic graphite electrodes for t-butyl hydroperoxide reduction at 1000 rpm in anaerobic 50 mM potassium phosphate buffer, 0.1 M NaCl, pH 7.0 at 25 °C. Reprinted with permission from the American Chemical Society, Ref. [47], copyright 2009...

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