8.10 : Oxidation of Alkenes: Syn Dihydroxylation with Osmium Tetraoxide

Alkenes are converted to 1,2-diols or glycols through a process called dihydroxylation. It involves the addition of two hydroxyl groups across the double bond with two different stereochemical approaches, namely anti and syn. Dihydroxylation using osmium tetroxide progresses with syn stereochemistry.

Syn Dihydroxylation Mechanism

The reaction comprises a two-step mechanism. It begins with the addition of osmium tetroxide across the alkene double bond in a concerted manner forming a five-membered cyclic osmate ester as an intermediate, which can be isolated and characterized. Osmium tetroxide is electrophilic in nature, serving as a strong oxidizing agent. It accepts an electron pair from the alkene π bond undergoing a reduction from +VIII to +VI.

In the next step,  the cyclic osmate ester reacts with a reducing agent like sodium bisulfite that cleaves the Os–O bond producing a cis-glycol with retention of the syn stereochemistry of the two newly formed C–O bonds.

A major drawback of the method is the use of toxic and expensive osmium tetroxide. To overcome this, osmium tetroxide is often used as a catalyst along with the co-oxidants like N-methylmorpholine N-oxide (NMO) or tert-butyl hydroperoxide (TBHP). The co-oxidants reoxidize the osmium +VI species to +VIII, thereby regenerating osmium tetroxide for further oxidation of the remaining alkenes.

Stereochemical Outcome

As oxidation of alkenes using osmium tetroxide is a stereospecific syn addition process, the two oxygens of osmium tetroxide are simultaneously added to the same face of the alkene π bond. Based on this, dihydroxylation of (E)-hex-3-ene produces a pair of enantiomers, while (Z)-hex-3-ene gives a meso compound.

Sharpless Asymmetric Dihydroxylation

Interestingly, Karl Barry Sharpless developed an enantioselective method for syn dihydroxylation of alkenes, for which he was awarded the Nobel prize. This method is known as Sharpless asymmetric dihydroxylation that is carried out using osmium tetroxide, a stoichiometric amount of the co-oxidant, and a chiral amine ligand.