What is Woodward Reaction Mechanism and How Does It Form Cis Diols
Hydroxylation of Alkenes
Converting an alkene to a glycol requires adding a hydroxy group to each end of the double bond. This addition is called dihydroxylation (or hydroxylation) of the double bond. Hydroxylation of Alkenes is the oxidation of an organic compound. When oxygen is added to the C-H group and forms a bond, there is a generation of -OH groups creating COH. As oxygen reacts very slowly, there is a need for catalysts or enzymes that are also termed as Hydroxylases. Let's take a look at a hydroxylation of alkenes example.
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Different Methods of Hydroxylation
The main methods of effecting cis-hydroxylation are by reaction with potassium permanganate, with osmium tetroxide alone or as a catalyst, or with silver iodoacetate according to Woodward procedure. The most basic method of trans-hydroxylation is undoubtedly the reaction with peracids. However, the Prevost reaction and oxidation with hydrogen peroxide in alkaline solution or the presence of specific oxide catalysts are also useful procedures. The different ways of hydroxylation of alkenes are as follows.
Hydroxylation using potassium permanganate.
Hydroxylation using osmium tetroxide.
Non-catalytic cis- Hydroxylation of Olefins using ester complexes.
Catalytic Cis-Hydroxylation of Olefins with Hydrogen Peroxide.
Catalytic Cis-Hydroxylation of Olefins with Metal Chlorates.
Catalytic Cis-Hydroxylation of Olefins with Sodium Hypochlorite.
Catalytic Cis-Hydroxylation of Olefins with tert-Butyl Hydroperoxide.
Catalytic Cis-Hydroxylation of Olefins with N-methyl morpholine N-oxide.
Catalytic Cis-Hydroxylation of Olefins with Oxygen or Air.
Hydroxylation using Organic peroxy acids
Hydroxylation using hydrogen Peroxide
Hydroxylation using halogens and silver carboxylates
Woodward Reaction
Now that you understand the concept of Hydroxylation of Alkenes, we will look at Woodward reaction. Robert Burns Woodward, an American organic chemist, invented the Woodward reaction. It is a known fact that every Alkaline compound has one or more Hydroxy group present in it. Now, when these compounds are in contact with silver acetate and Iodine, they release 'syn-diols' or 'cys-diols'. The 'Syn-diols/cys-diols' are twin -OH group that is, two Hydroxy groups adjacent with the carbons. As there is a displacement of the nucleophile, this would result in the desired form of diols. This is just opposite to a Prevost reaction as it means to remove the 'anti-diols' in the presence of Iodine and any benzoate and absence of water. Hence, we can conclude that Woodward reaction is just a modification of Prevost reaction that deals with the addition of 'syn' instead of removal. Let us try to understand it elaborately with the help of an example, as shown below.
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The image shows the cis-hydroxylation Woodward reaction, wherein an alkene reacts with silver nitrate and Iodine to form cis-diols. It is similar to the Prevost reaction.
Woodward Reaction Mechanism
In the Woodward reaction first addition of Iodine happens with alkenes, then in the presence of water, a nucleophilic displacement with acetate occurs. Thus, we get syn-diols. When the intermediate ester gets hydrolysed, we get the desired diol.
Intermediate Steps of the Mechanism are Listed Below:
First, Iodine and alkene react with each other and form a cyclic intermediate.
Again, the iodonium cyclic intermediate and acetate ion start a reaction in SN2 fashion and form a ring compound of five members.
Hydrolysis reaction opens the five-membered rings.
Next, protonation of the compound takes place followed by a hydrolysis reaction. As a result, we get diols.
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Solved Problems
Question 1) The Steroid (I) Reacts with OsO4/H2O2 to Give (II) as the Major Product of 80%. Explain?
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Answer 1) The dihydroxylation may be stereospecific with respect not only to the double bond but also to other stereocenters in the substance. In the case of steroid (I) the α-face of the molecule is less sterically hindered to result in vicinal diol formation on the α-side of the molecule.
Question 2) What Happens When the Following Compounds React with OsO4/H2S.
a) (Z)-3-hexene.
b) (E)-3-hexene.
Answer 2) The chemical reactions for the following compounds are as follows.
a) When (Z)-3-hexene reacts with OsO4/H2S, Meso-3,4-hexanediol is formed due to the hydroxylation of alkenes. There are two stereocenters in this reaction.
b) When (E)-3-hexene reacts with OsO4/H2S, A racemic mixture of 3,4-hexanediol is formed. There are two stereocenters in both products.
Applications of Woodward Reaction
The Woodward reaction is used in organic chemistry and steroid chemistry.
It is used to synthesize various forms of alkenes.
It is used to produce long-chain olefinic compounds.
FAQs on Woodward Reaction in Organic Chemistry
1. What is the Woodward reaction in organic chemistry?
The Woodward reaction is a chemical reaction that converts alkenes into cis-1,2-diols using iodine and silver acetate in the presence of water. It is also called the Woodward cis-hydroxylation and is commonly used to achieve syn-dihydroxylation of alkenes. The reaction proceeds through the formation of an iodonium intermediate followed by nucleophilic attack and hydrolysis, ultimately giving a vicinal diol with cis stereochemistry.
2. What reagents are used in the Woodward reaction?
The Woodward reaction uses iodine (I2), silver acetate (AgOAc), and water as the main reagents. These components work together as follows:
- I2 forms an iodonium ion intermediate with the alkene.
- AgOAc helps generate the reactive species and removes iodide as AgI(s).
- Water participates in hydrolysis to form the final cis-diol.
This reagent system distinguishes the Woodward reaction from other alkene hydroxylation methods.
3. What is the mechanism of the Woodward reaction?
The mechanism of the Woodward reaction involves formation of an iodonium ion intermediate followed by nucleophilic substitution and hydrolysis to give a cis-diol. The key steps are:
- Formation of a cyclic iodonium ion when the alkene reacts with I2.
- Nucleophilic attack by acetate ion (from AgOAc), opening the ring.
- Subsequent substitution and hydrolysis in the presence of water.
- Removal of iodide as insoluble AgI(s), driving the reaction forward.
The overall result is syn addition of two hydroxyl groups across the double bond.
4. What is the product of the Woodward reaction?
The product of the Woodward reaction is a cis-1,2-diol (vicinal diol) formed by syn addition across an alkene double bond. For example:
- Ethene → Ethane-1,2-diol (ethylene glycol)
Both hydroxyl (–OH) groups are added to the same side of the double bond, giving cis stereochemistry, which is the defining feature of the Woodward hydroxylation.
5. What is the difference between the Woodward reaction and the Prévost reaction?
The key difference is that the Woodward reaction gives cis-diols, while the Prévost reaction gives trans-diols. The distinction arises from reaction conditions:
- Woodward reaction: I2, AgOAc, and water → cis-1,2-diol (syn addition).
- Prévost reaction: I2 and AgOAc under anhydrous conditions → trans-1,2-diol (anti addition after hydrolysis).
Thus, the presence or absence of water controls the stereochemical outcome.
6. Is the Woodward reaction a syn or anti addition?
The Woodward reaction is a syn addition reaction that produces cis-diols. Both hydroxyl groups are added to the same face of the alkene due to the reaction pathway involving intramolecular substitution and hydrolysis in the presence of water. This syn stereochemistry differentiates it from anti-dihydroxylation reactions.
7. Why is silver acetate used in the Woodward reaction?
Silver acetate is used to generate acetate ions and remove iodide as insoluble AgI(s), driving the reaction forward. Its roles include:
- Providing acetate (OAc−) as a nucleophile.
- Reacting with iodide to form AgI(s), which precipitates.
- Facilitating formation of the reactive iodonium intermediate.
Without AgOAc, the reaction would not proceed efficiently toward cis-diol formation.
8. Can you give an example of the Woodward reaction?
A common example of the Woodward reaction is the conversion of cyclohexene into cis-1,2-cyclohexanediol using I2, AgOAc, and water. The transformation can be summarized as:
- Cyclohexene → cis-1,2-cyclohexanediol
The two –OH groups are added to adjacent carbons on the same side of the ring, demonstrating cis hydroxylation of alkenes.
9. What type of reaction is the Woodward reaction?
The Woodward reaction is an electrophilic addition reaction followed by nucleophilic substitution and hydrolysis. It involves:
- Electrophilic addition of iodine to an alkene.
- Formation of a cyclic iodonium ion intermediate.
- Nucleophilic attack and hydrolysis to form a vicinal diol.
Overall, it is classified as a dihydroxylation reaction of alkenes with syn stereochemistry.
10. What are the key features to remember about the Woodward reaction?
The key features of the Woodward reaction are cis-diol formation, use of iodine and silver acetate, and syn addition across alkenes. Important points include:
- Reagents: I2, AgOAc, and water.
- Product: cis-1,2-diol (vicinal diol).
- Stereochemistry: syn addition.
- Intermediate: cyclic iodonium ion.
- Comparison: Opposite stereochemistry to the Prévost reaction.
These features make it a standard method for cis-hydroxylation of alkenes in organic synthesis.
