8.10 : Oxidation of Alkenes: Syn Dihydroxylation with Osmium Tetraoxide

Dihydroxylation is an oxidative addition reaction, where two hydroxyl groups are added across a carbon–carbon double bond to form 1,2-diols or glycols.

Dihydroxylation of alkenes can be carried out by two different stereochemical routes: anti dihydroxylation and syn dihydroxylation.

In syn dihydroxylation, an alkene is treated with osmium tetroxide in pyridine, forming a cyclic osmate ester, followed by reduction with aqueous sodium bisulfite to give a cis-diol along with the reduced form of osmium tetroxide.

The mechanism is a two-step process that begins with the addition of osmium tetroxide across the alkene double bond in a concerted manner to form a five-membered cyclic osmate ester.

Osmium tetroxide is a strong oxidizing agent and electrophilic in nature. It readily accepts electrons from the alkene π bond, thereby reducing the oxidation state of osmium from +8 to +6.

The two oxygen atoms add simultaneously across the same face of the alkene double bond with syn stereochemistry.

In the second step, the osmate ester is hydrolyzed in the presence of sodium bisulfite, which cleaves the osmium–oxygen bond without altering the stereochemistry of the carbon–oxygen bond to form a cis-diol.

Although the reaction is stereospecific and produces cis-diols in good yields, the use of osmium tetroxide is limited because it is very toxic and expensive.

To overcome these limitations, typical co-oxidants like N-methylmorpholine N-oxide or tert-butyl hydroperoxide are added to the reaction mixture.

The co-oxidant oxidizes osmium +6 to +8 and regenerates the osmium tetroxide for oxidation of the remaining alkenes.

Since the reaction is stereospecific, the syn dihydroxylation of (E)-hex-3-ene forms a pair of enantiomers, whereas the syn dihydroxylation of (Z)-hex-3-ene forms one product, which is a meso compound.

A friendlier enantioselective method for syn dihydroxylation of alkenes was developed by Karl Barry Sharpless, for which he was awarded the Nobel prize. The reaction is carried out in the presence of chiral amine ligands and is referred to as Sharpless asymmetric dihydroxylation.