Anti-1 -Alkene-3,4-diols

Diols can be prepared either by direct hydroxylation of an alkene with 0s04 followed by reduction with NaHSOj or by acid-catalyzed hydrolysis of an epoxide (Section 7.8). The 0s04 reaction occurs with syn stereochemistry to give a cis diol, and epoxide opening occurs with anti stereochemistry to give a trans diol. 

Diastereoselectivity has been observed in oxymercuration of alkenes having nearby oxygen substituents. Terminal allylic alcohols show a preference for formation of the anti 2,3-diols. 

Attack has been shown on only one of the two possible carbon atoms in (49) and (50), though on different ones in the two cases. Attack on the other carbon, in each case, will lead to the same product, the meso 1,2-diol (51). By comparing the configuration of (51) with that of the original alkene (48b), it will be seen that—in overall terms— stereoselective ANTI hydroxylation has been effected. 

Some drugs fall within the class of functionalized alkenes discussed here. Thus, the anti-inflammatory agent alclophenac (10.63) contains an O-allyl group. Its epoxide was found as a stable metabolite in the urine of mice and humans, and so was the diol, proving the involvement of the epoxide-diol pathway in the metabolism of this drug. The epoxide proved mutagenic, but only in the absence of a rat liver S-9 suspension (which contains EH) [141]. 

Anti-hydroxylation of alkenes preparation of ontr-diols... 

Alkenes react with peroxyacids (RCO3H) followed by hydrolysis to give trans-1,2-diols. The products are always anft-diols, since the reaction occurs with anti addition. 

Alkenes may also react with certain oxidizing agents to result in anti hydroxyla-tion. Treatment with peroxycarboxylic acids435 leads initially to an epoxide. Ring scission of the latter via an SN2 reaction in an anti manner with the corresponding carboxylic acid or water gives the trans monoester or tram diol, respectively. Complete anti stereoselectivity and high yields in the oxidation of cycloalkenes are... 

Since H202 is easier to handle than 02, we will focus on the use of the former. Many metals can be used for this transformation [50]. Among them, iron compounds are of interest as mimics of naturally occurring non-heme catalysts such as methane monooxygenase (MMO) [51a] or the non-heme anti-tumor drug bleomycin [51b]. Epoxidation catalysts should meet several requirements in order to be suitable for this transformation [50]. Most importantly they must activate the oxidant without formation of radicals as this would lead to Fenton-type chemistry and catalyst decomposition. Instead, heterolytic cleavage of the 0—0 bond is desired. In some cases, alkene oxidation furnishes not only epoxides but also diols. The latter transformation will be the topic of the following section. 

Acid-catalyzed hydrolysis of the epoxide yields a diol its stereochemistry corresponds to net anti hydroxylation of the double bond of the original alkene. 

The Prevost Reaction allows the synthesis of anti-diols from alkenes by the addition of iodine followed by nucleophilic displacement with benzoate in the absence of water. Hydrolysis of the intermediate diester gives the desired diol.The Woodward Modification of the Prevost Reaction gives syn-diols. 

Dihydroxylation of an alkene with 0s04 is a specifically cis reaction the two OH groups add to the same side of the alkene. So E-22 gives one diastereomer (syn as drawn) of the diol 23 while Z-22 gives, by syn addition, a diol that can be re-drawn after rotation of a bond, as anti -23. 

However, should you wish to make both syn and anti-diols from an alkene when only one isomer (E- or Z-) can be made, such as cyclopentene 25, you need another method. Epoxidation... 

Anti hydroxylation of an alkene is readily achieved with peroxycarboxylic adds. Add-catalyzed ring opening of the irutial produd, an oxirane (epoxide), forms the monoester of a 1,2-diol, hydrolysis of which affords the parent diol. Alternative reagents whi ate often used for anti hydroxylation of alkenes are hydrogen peroxide with oxides of tungsten > 4.2i gj. selenium, 444i and iodine-silver benzoate (Pr6vost reaction).. ... 

Because one OH group of the 1,2-diol comes from the epoxide and one OH group comes from the nucleophile ( OH), the overall result is anti adflition of two OH groups to an alkene. 

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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