Syn Hydroxylation of Alkenes

Osmium tetroxide (OSO4, sometimes called osmic acid) reacts with alkenes in a concerted Step to form a cyclic osmate ester. Hydrogen peroxide hydrolyzes the osmate ester and reoxidizes osmium to osmium tetroxide. The regenerated osmium tetroxide catalyst continues to hydroxylate more molecules of the alkene. 

Because the two carbon—oxygen bonds are formed simultaneously with the cyclic osmate ester, the oxygen atoms add to the same face of the double bond that is, they add with syn stereochemistry. The following reactions show the use of OSO4 and H2O2 for the syn hydroxylation of alkenes. 

In addition to its synthetic value, the permanganate oxidation of alkenes provides a simple chemical test for the presence of an alkene. When an alkene is added to a clear, deep purple aqueous solution of potassium permanganate, the solution loses its purple color and becomes the murky, opaque brown color of Mn02-(Although there are other functional groups that decolorize permanganate, few do it as quickly as alkenes.) 

To hydroxylate an alkene with syn stereochemistry, which is the better reagent osmium tetroxide or potassium permanganate Osmium tetroxide gives better yields, but permanganate is cheaper and safer to use. The answer depends on the circumstances. 

Predict the major products of the following reactions, including stereochemistry. 

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Syn-hydroxylation of alkenes is also effected by a catalytic amount of osmium tetroxide in the presence of hydrogen peroxide. Originally developed by Milas, the reaction can be performed with aqueous hydrogen peroxide in solvents such as acetone or diethyl ether.58 Allyl alcohol is quantitatively hydroxylated in water (Eq. 3.12).59... 

Several related procedures for syn hydroxylation of alkenes involve a halohydrin ester (32) as the key intermediate. In Woodward s procedure an alkene in glacial acetic acid is treated with iodine and silver acetate. Acetyl hypoiodite, MeCOjI, formed by reaction of the latter two reagents attacks the alkene, R R 0=CR R in an electrophilic manner, from the less hindered side to give, by overall anti addition. 

For the oxidation of alkenes, osmium tetroxide is used either stoichiometrically, when the alkene is precious or only small scale operation is required, or catalytically with a range of secondary oxidants which include metal chlorates, hydrogen peroxide, f-butyl hydroperoxide and N-methylmorpholine A -oxide. The osmium tetroxide//V-methylmorpholine A -oxide combination is probably the most general and effective procedure which is currently available for the syn hydroxylation of alkenes, although tetrasubstituted alkenes may be resistant to oxidation. For hindered alkenes, use of the related oxidant trimethylamine A -oxide in the presence of pyridine appears advantageous. When r-butyl hydroperoxide is used as a cooxidant, problems of overoxidation are avoided which occasionally occur with the catalytic procedures using metal chlorates or hydrogen peroxide. Further, in the presence of tetraethylam-monium hydroxide hydroxylation of tetrasubstituted alkenes is possible, but the alkaline conditions clearly limit the application. 

Despite the development in recent years of new reagents for organic synthesis, osmium tetroxide, used either stoichiometrically or catalydcally, remains the reagent of choice for syn hydroxylation of alkenes. " Surprisingly, the hydroxylation of alkynes to give " > 1,2-dicarfoonyl compounds has been much less studied, but it has considerable potential for use in the synthesis of complex molecules. 

The syn-hydroxylation of alkenes can also be effected by hydrogen peroxide in presence of catalytic amount of OsO. This procedure was used earlier in solvents such as acetone or diethyl ether. By this method allyl alcohol is quantitatively hydroxylated in water (Scheme-70)." ... 

Overall the reaction leads to addition of two hydroxyl groups to the double bond and IS referred to as hydroxylation Both oxygens of the diol come from osmium tetraox ide via the cyclic osmate ester The reaction of OSO4 with the alkene is a syn addition and the conversion of the cyclic osmate to the diol involves cleavage of the bonds between oxygen and osmium Thus both hydroxyl groups of the diol become attached to the same face of the double bond syn hydroxylation of the alkene is observed... 

Potassium permanganate, usually in alkaline conditions, using aqueous or aqueous-organic solvents, is a widely used oxidant for effecting syn-vicinal hydroxylation of alkenes (Eq. 3.13). However, overoxidation or alternative oxidation pathways may pose a problem, and the conditions must be carefully controlled.62... 

Thus by suitable choice of reagent, the hydroxylation of alkenes can be made stereoselectively SYN or ANTI at will. 

Hydroxylation of alkenes is the most important method for the synthesis of 1,2-diols (also called glycol). Alkenes react with cold, dilute and basic KMn04 or osmium tetroxide (OSO4) and hydrogen peroxide to give cis-1,2-diols. The products are always syn-diols, since the reaction occurs with syn addition. 

Hydroxylation of alkenes using osmium tetraoxide is a syn addition of hydroxyl groups to the double bond. ds-2-Butene yields the meso diol. 

Hydroxylation of alkenes with osmium tetraoxide is a syn addition. A racemic mixture of the 2R,3S... 

Compounds J and L have the same molecular formula, C7H1402, but J is a liquid and L is a crystalline solid. Their molecular formulas correspond to the addition of two OH groups to compound I. Osmium tetraoxide brings about syn hydroxylation of an alkene therefore compound J must be the cis diol. 

The diol can be prepared from syn hydroxylation of (Z)-2-butene. The c/s-alkene can be prepared by hydrogenation of 2-butyne, and 2-butyne can be prepared by alkylation of propyne. The retrosynthetic analysis is ... 

The 1 1 complex b ween bovine serum and an osmate ester is an enantioselective catalyst in the syn hydroxyladon of certain alkenes, although synthetic applications iq>pear to be limited. Asymmetric di-hydroxylation of alkenes is considered in a review on catalytic asymmetric reactions. ... 

Since silver salts are expensive, other cheaper reagents have been sought which can bring about the same type of conversion, and the iodine- tassium iodate- tassium acetate combination has been found to provide a useful alternative. Thallium(I) acetate may be used in place of silver acetate in the Woodward procedure, and syn hydroxylation of steroidal alkenes with dialliumflll) acetate in acetic acid has been performed. ... 

With careful choice of reagent and reaction conditions, alkenes containing other functionalities can be selectively hydroxylated without complicating side reactions. For example, the oxidation may be carried out in the presence of ester, ether, sulfide, carboxylic acid, acetal, carbonyl, halo, alcohol and aryl groups. Regioselective hydroxylation is also possible in dienes in which one center is electron poor, and some selectivity is also found between isolated double bonds. For example, syn hydroxylation of diene (5) with a catalytic amount of osmium tetroxide and N-methylmorpholine N-oxide as the secondary oxidant gives diol (6) in 46% yield, and phase transfer catalyzed permanganate oxidation of diene (7) affords diol (8) in 83% yield. 

Hydrolysis of the ester does not change the configuration. The Woodward modification of the Prevost reaction is similar, but results in overall syn hydroxylation. The alkene is treated with iodine and silver acetate in a 1 1 molar ratio in acetic acid containing water. Here again, the initial product is a (3-halo ester the addition is anti and a nucleophilic replacement of the iodine occurs. However, in the presence of water, neighboring-group participation is prevented or greatly decreased by solvation of the ester function, and the mechanism is the normal Sn2 process, ... 

Both complexes are used in the hydroxylation of double bonds via diacetates or dibenzoates of vicinal diols. The reaction is stereospecific. In anhydrous medium (the Privost reaction [783]), the reaction takes place in the anti mode. In the presence of water (the Woodward modification [783]), the reaction results in a syn addition. The mechanisms of both reactions are shown in the section Hydroxylation of Alkenes and Cycloal-kenes in Chapter 3 see equation 78). 

Hydroxylation, the addition of two hydroxyl groups across double bonds, converts alkenes and cycloalkenes into vicinal dials. Stereochem-ically. the addition may occur in the syn or the anti mode. In open-chain alkenes (with the exception of terminal alkenes for which stereochemistry is irrelevant), syn hydroxylation transforms cis alkenes into erythro (or meso) diols and trans alkenes into threo (or dl) diols. anti Hydroxylation of cis alkenes gives threo (or dl) diols, whereas anti hydroxylation of trans alkenes yields erythro (or meso) diols. syn Hydroxylation of cycloalkenes gives cis diols, whereas anti hydroxylation furnishes trans diols (Table I). 

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