2,3-Epoxy primary alcohols, oxidation

Metals that are capable of 2e redox changes, typically main group elements and 4d and 5d transition metals, can give heterolysis of a peroxide to form a diamagnetic oxidant that may avoid the radical pathways seen in the case of equation (14-15). O atom transfer to the substrate is possible in this way. Sharpless epoxidation provides an excellent example. In this case rBuOOH is the primary oxidant, Ti(i-OPr)4 is the catalyst precursor and a tartrate ester is the ligand that induces a high ee in the epoxy alcohol formed from an allylic alcohol. This reaction has been successfiiUy developed on an industrial scale. 

The primary oxidation products (hydroperoxides) are unstable and susceptible to decomposistion. A complex mixture of volatile, nonvolatile, and polymeric secondary oxidation products is formed through decomposition reactions, providing various indices of lipid oxidation (5). Secondary oxidation products include aldehydes, ketones, alcohols, hydrocarbons, volatile organic acids, and epoxy compounds, among others. Methods for assessing lipid oxidation based on their formation are discussed in this section. 

The first practical method for asymmetric epoxidation of primary and secondary allylic alcohols was developed by K.B. Sharpless in 1980 (T. Katsuki, 1980 K.B. Sharpless, 1983 A, B, 1986 see also D. Hoppe, 1982). Tartaric esters, e.g., DET and DIPT" ( = diethyl and diisopropyl ( + )- or (— )-tartrates), are applied as chiral auxiliaries, titanium tetrakis(2-pro-panolate) as a catalyst and tert-butyl hydroperoxide (= TBHP, Bu OOH) as the oxidant. If the reaction mixture is kept absolutely dry, catalytic amounts of the dialkyl tartrate-titanium(IV) complex are suflicient, which largely facilitates work-up procedures (Y. Gao, 1987). Depending on the tartrate enantiomer used, either one of the 2,3-epoxy alcohols may be obtained with high enantioselectivity. The titanium probably binds to the diol grouping of one tartrate molecule and to the hydroxy groups of the bulky hydroperoxide and of the allylic alcohol... 

Fig. 2.2 Oxidation of a primary long-chain alcohol by TRAP with retention of its epoxy linkage [16]...

Oxidations. The reagent 1 oxidizes primary and secondary alcohols to carbonyl compounds in fair to good yield. It is not useful for epoxidation of simple alkenes, but it epoxidizes allylic alcohols to form a,/ -epoxy alcohols in 60-70% yield, In general, this epoxidation is more stcreospccific than that observed with r-butyl hydroperoxide in combination with Mo(CO)6 (9, 81-82). 

In order to prevent competing homoallylic asymmetric epoxidation (AE, which, it will be recalled, preferentially delivers the opposite enantiomer to that of the allylic alcohol AE), the primary alcohol in 12 was selectively blocked as a thexyldimethylsilyl ether. Conventional Sharpless AE7 with the oxidant derived from (—)-diethyl tartrate, titanium tetraisopropoxide, and f-butyl hydroperoxide next furnished the anticipated a, [3-epoxy alcohol 13 with excellent stereocontrol (for a more detailed discussion of the Sharpless AE see section 8.4). Selective O-desilylation was then effected with HF-triethylamine complex. The resulting diol was protected as a base-stable O-isopropylidene acetal using 2-methoxypropene and a catalytic quantity of p-toluenesulfonic acid in dimethylformamide (DMF). Note how this blocking protocol was fully compatible with the acid-labile epoxide. 

When an unsymmetrical secondary alcohol is formed, depending on which carbon-oxygen bond is cleaved. With propylene oxide, for example, a base-catalyzed reaction favors the formation of the secondary alcohol almost exclusively, whereas, a non-catalytic or acid-catalyzed alcoholysis yields a mixture of the isomeric ethers. However, the reactions of other a-epoxides, such as 3,4-epoxy-l-butene, 3,4-epoxy-l-chloropropane (epichlorohydrin), 3,4-epoxy-l-propanol (glycidol), and styrene oxide, are more complicated with respect to which isomer is favored. ... 

As oxidation normally proceeds very slowly at the initial stage, the time to reach a sudden increase in oxidation rate is referred to as the induction period (6). Lipid hydroperoxides have been identified as primary products of autoxidation decomposition of hydroperoxides yields aldehydes, ketones, alcohols, hydrocarbons, volatile organic acids, and epoxy compounds, known as secondary oxidation products. These compounds, together with free radicals, constitute the bases for measurement of oxidative deterioration of food lipids. This chapter aims to explore current methods for measuring lipid oxidation in food lipids. 

The most important applications of peroxyacetic acid are the epoxi-dation [250, 251, 252, 254, 257, 258] and anti hydroxylation of double bonds [241, 252, the Dakin reaction of aldehydes [259, the Baeyer-Villiger reaction of ketones [148, 254, 258, 260, 261, 262] the oxidation of primary amines to nitroso [iJi] or nitrocompounds [253], of tertiary amines to amine oxides [i58, 263], of sulfides to sulfoxides and sulfones [264, 265], and of iodo compounds to iodoso or iodoxy compounds [266, 267] the degradation of alkynes [268] and diketones [269, 270, 271] to carboxylic acids and the oxidative opening of aromatic rings to aromatic dicarboxylic acids [256, 272, 271, 272,273, 274]. Occasionally, peroxyacetic acid is used for the dehydrogenation [275] and oxidation of aromatic compounds to quinones [249], of alcohols to ketones [276], of aldehyde acetals to carboxylic acids [277], and of lactams to imides [225,255]. The last two reactions are carried out in the presence of manganese salts. The oxidation of alcohols to ketones is catalyzed by chromium trioxide, and the role of peroxyacetic acid is to reoxidize the trivalent chromium [276]. 

In contrast to the lack of selectivity observed in the TS-1 catalyzed oxidation of 3-penten-2-ol (1) (Eqn. 21.5), the oxidation of 1 with tert-butyl hydroperoxide (TBHP) over Cr-PILC gave the unsaturated ketone, 3, in 82% yield (Eqn. 21.13)42 while the oxidation of 1 over a vanadium pillared montmorillonite (V-PILC) gave the epoxy alcohol, 2, in 94% yield.43 V-PILC, however, does promote the oxidation of primary benzyl alcohols to the acids with tert-butyl hydroperoxide. This reaction exhibits shape selectivity in that para-substituted benzyl alcohols are oxidized while the ortho- and meta- substituted species are essentially inert (Eqn. 21.14).44... 

Ogawa later published the synthesis of a 3-amino-3,4-dideoxyhexiu-onic acid in route to ezomycin [24]. In that account, a 1,6-anhydro epoxy sugar was reacted with sodium azide followed by antimony pentachloride to give methyl 3-azido-2-0-benzoyl-a-D-glucospyranoside. Oxidation of the primary alcohol was achieved with potassium permanganate, and reduction of the azide was accomplished with hydrogenation (Fig. 8). 

The synthetic utility of (i )-enoate 392 is illustrated in the stereoselective synthesis of the bengamide E derivative 399 (Scheme 88). Silyl protection of 392, reduction with DIBAL, and Sharpless epoxidation of the resulting allylic alcohol furnishes epoxy alcohol 396 as a 95 5 anti syn mixture. Conversion of the primary hydroxyl group of 396 to an iodide under neutral conditions followed by a metallation-elimination and subsequent in situ methylation provides the ether 397. Ozonolysis, desilylation with aqueous acetic acid, and a Dess-Martin oxidation supplies the a,jS-dialkoxy aldehyde 398. This, utilizing stannane Se addition, is then converted to 399 [135]. 

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