Name: alkene dihydroxylation with osmium tetroxide
Uploaded: 2025-05-22T09:05:34.000Z
Duration: 2 min 44 s
Channel: JoVE

Dihydroxylation is an oxidative addition reaction, where two hydroxyl groups are added across a carbon&#8211;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 &#960; 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&#8211;oxygen bond without altering the stereochemistry of the carbon&#8211;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.

oxidation of alkenes: syn dihydroxylation with osmium tetraoxide

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.
<img alt="Cyclohexene oxidation reaction, OsO4, NaHSO3; chemical equation diagram, organic synthesis process." src="/files/ftp_upload/11781/11781_PT_Figure_1.svg" style="text-align: center; height: 60px;" data-altupdatedat="1754904545000" data-alt="Cyclohexene dihydroxylation reaction mechanism, chemical equation, reagent diagram." />
<h4>Syn Dihydroxylation Mechanism</h4>
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 &#960; 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&#8211;O bond producing a cis-glycol with retention of the syn stereochemistry of the two newly formed C&#8211;O bonds.
<img alt="Organic reaction diagram; reagent arrows, structural formulas, sulfonate synthesis steps." src="/files/ftp_upload/11781/11781_PT_Figure_2.svg" style="text-align: center; height: 200px;" data-altupdatedat="1754904545000" data-alt="Organic reaction mechanism diagram; stepwise cycloaddition with reagent NaHSO3." />
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.
<h4>Stereochemical Outcome</h4>
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 &#960; bond. Based on this, dihydroxylation of (E)-hex-3-ene produces a pair of enantiomers, while (Z)-hex-3-ene gives a meso compound.
<img alt="Syn dihydroxylation reaction diagram; alkene to diol formation with stereochemistry shown." src="/files/ftp_upload/11781/11781_PT_Figure_3.svg" style="text-align: center; height: 130px;" data-altupdatedat="1754904545000" data-alt="Syn dihydroxylation process; chemical reaction diagram; showing reagent conversion; organic chemistry." />
<h4>Sharpless Asymmetric Dihydroxylation</h4>
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. 
<img alt="Chemical reaction diagram; asymmetric dihydroxylation process; AD-mix-&#945;/&#946;; stereochemistry." src="/files/ftp_upload/11781/11781_PT_Figure_4.svg" style="text-align: center; height: 60px;" data-altupdatedat="1754904545000" data-alt="Organic reaction diagram; enantiomer synthesis using AD-mix; chemical equations; 0&#176;C condition." />

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 ...

oxidation-of-alkenes-syn-dihydroxylation-with-osmium-tetraoxide

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Organic Chemistry

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Reactions of Alkenes

KEY TERMS AND CONCEPTS

alkene dihydroxylation with osmium tetroxide

Alkene dihydroxylation with osmium tetroxide adds two hydroxyl groups across a double bond to make 1,2-diols, also called glycols. The reaction can give either anti or syn products, and this method follows syn stereochemistry. That means both new O atoms add to the same face of the alkene.

The reaction occurs in two steps. First, osmium tetroxide adds to the alkene double bond in a concerted step, where both bonds form at the same time. This creates a five-membered cyclic osmate ester intermediate, which can be isolated and characterized. Osmium tetroxide is electrophilic and acts as a strong oxidizing agent. It accepts an electron pair from the alkene pi bond and is reduced from +VIII to +VI.

In the second step, a reducing agent such as sodium bisulfite breaks the Os-O bond. This step produces a cis-glycol while keeping the syn arrangement of the two new C-O bonds. The product remains stereospecific because the oxygen atoms were added to the same face of the double bond.

A drawback of this method is that osmium tetroxide is toxic and expensive. To reduce this problem, it is often used as a catalyst with co-oxidants such as N-methylmorpholine N-oxide, or NMO, and tert-butyl hydroperoxide, or TBHP. These co-oxidants reoxidize osmium from +VI back to +VIII and regenerate osmium tetroxide for more alkene oxidation.

The stereochemical outcome depends on the alkene geometry. Oxidation of (E)-hex-3-ene gives a pair of enantiomers. Oxidation of (Z)-hex-3-ene gives a meso compound. Karl Barry Sharpless also developed an enantioselective version called Sharpless asymmetric dihydroxylation. It uses osmium tetroxide, a stoichiometric amount of co-oxidant, and a chiral amine ligand.

Alkene Dihydroxylation with Osmium Tetroxide

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Alkene dihydroxylation with osmium tetroxide adds two hydroxyl groups across a double bond to make 1,2-diols, also called glycols. The reaction can give either anti or syn products, and this method follows syn stereochemistry. That means both new O atoms add to the same face of the alkene. The reaction occurs in two steps. First, osmium tetroxide adds to the alkene double bond in a concerted step, where both bonds form at the same time. This creates a five-membered cyclic osmate ester...

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key terms and concepts

Learn how osmium tetroxide adds two hydroxyl groups to alkenes by syn dihydroxylation, including the cyclic osmate ester, stereochemistry, and Sharpless asymmetric dihydroxylation.

Alkene Dihydroxylation with Osmium Tetroxide | JoVE K12

organic chemistry

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Alkene Dihydroxylation with Osmium Tetroxide

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