Syn hydroxylation

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... 

In the previous section, we saw how to perform an anti addition of OH and OH across a double bond. In this section, we will explore the conditions that will allow us to perform a syn addition of OH and OH across a double bond. This reaction is often called a syn hydroxylation. 

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... 

Synthesis of 2,3-butanediol enantiomers syn-hydroxylation of trans-2-butene. Retrosvnthetic Analysis... 

The cis form has been prepared by the syn hydroxylation of cyclopentene by osmium tetroxide as follows ... 

Hydrolysis of the ester does not change the configuration. Woodward s method is similar, but results in overall syn hydroxylation. The olefin 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-... 

For another method of syn hydroxylation, which can be applied to cither face, see Corey Das Tetrahedron Lett. 1982, 23, 4217. 

KMnC>4 and OsC>4 have long been used to achieve syn hydroxylation of the carbon—carbon double bond. The syn stereoselectivity results from the formation of cyclic ester intermediates formed by addition of the reagent from the less hindered side of the double bond. 

Osmium tetraoxide hydroxylation is a method of achieving syn hydroxylation. The necessary starting material is ris-2-butene. 

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. 

Fig. syn-Hydroxylation with KMn04 The reaction works better with osmium tetroxide. However, this is a highly toxic and expensive reagent and has to be handled with care. 

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 ... 

Syn hydroxylation from the more hindered face of a ir-system can be effected using Woodward s pro-cedure in which an alkene is treated with iodine-silver acetate in acetic acid containing water. Variants of this method avoid the use of silver salts.A versatile pocedure by which syn hydroxyla-tion can be performed on either the more hindered or less hindered face of an alkene relies on stereoselective formation of the appropriate traru-bromohydrin from the alkene. ... 

Despite the development in recent years of new reagents for oi anic synthesis, osmium tetroxide, used either stoichiometrically or catalytically, remains the reagent of choice for syn hydroxylation of al kenes. Surprisingly, the hydroxylation of alkynes to give 1,2-dicarbonyl compounds has been much less studied, but it has considerable potential for use in the synthesis of complex molecules. 

Substituents occupying sites more remote from the alkenic center than the allylic position may also influence the direction of attack on an alkene with diastereotopic Tr-faces. Thus, cyclic alkenes with a sul-foximine group attached to an exocyclic homoallylic carbon atom and a hydroxy group at the allylic position, for example (Iti) in equation (5), undergo syn hydroxylation with a very high degree of dia-stereoselectivity, diol (17) being produced as the sole diastereoisomer. ... 

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. 

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. ... 

Syn hydroxylation is most commonly performed using osmium tetroxide or potassium permanganate, and addition usually occurs from the less hindered side of the double bond in the absence of other directing effects. With Aese reagents, the stereospecificity of syn addition results from formation of cyclic ester intermediates. Support for these arises from isolation of solid addition complexes (1) on reaction of... 

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. 

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. 

The 1 1 complex between bovine serum and an osmate ester is an enantioselective catalyst in the syn hydroxylation of certain alkenes, although synthetic applications appear to be limited. Asynunetric dihydroxylation of alkenes is considered in a review on catalytic asymmetric reactions. ... 

---