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.
[Image will be Uploaded Soon]
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.
[Image will be Uploaded Soon]
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.
[Image will be Uploaded Soon]
Solved Problems
Question 1) The Steroid (I) Reacts with OsO4/H2O2 to Give (II) as the Major Product of 80%. Explain?
[Image will be Uploaded Soon]
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
1. What is the Woodward reaction in organic chemistry?
The Woodward reaction, also known as Woodward cis-hydroxylation, is a chemical method used to convert an alkene into a cis-diol (or syn-diol). This transformation is achieved by reacting the alkene with iodine (I₂) and silver acetate (CH₃COOAg) in the presence of wet acetic acid, which contains water. The key outcome is the addition of two hydroxyl (-OH) groups to the same face of the original double bond, resulting in a syn-stereochemical product.
2. What is the main difference between the Woodward reaction and the Prévost reaction?
The primary difference lies in the reaction conditions and the resulting stereochemistry of the diol product.
- Woodward Reaction: This reaction is carried out in the presence of water. It produces a syn-diol (or cis-diol), where the two hydroxyl groups are on the same side of the molecule.
- Prévost Reaction: This reaction is conducted under anhydrous (dry) conditions. It produces an anti-diol (or trans-diol), where the two hydroxyl groups are on opposite sides of the molecule.
3. How does the Woodward reaction compare to syn-hydroxylation using Osmium Tetroxide (OsO₄)?
Both the Woodward reaction and oxidation with Osmium Tetroxide (OsO₄) are methods to produce syn-diols from alkenes. However, their mechanisms differ, which can lead to opposite stereochemical outcomes in complex, sterically hindered molecules. While OsO₄ addition typically occurs on the less hindered face of the alkene, the multi-step mechanism of the Woodward reaction can sometimes result in the final hydroxyl groups being delivered to the more hindered face, reversing the stereoselectivity.
4. Why is water a critical component for achieving cis-dihydroxylation in the Woodward reaction?
Water plays a crucial role as a nucleophile in the reaction mechanism. After the formation of an initial cyclic intermediate, water attacks it to form a hydroxy-ester. This step is key to setting the final stereochemistry. The subsequent hydrolysis of this ester intermediate yields the syn-diol product. In the absence of water (as in the Prévost reaction), a different mechanistic pathway is followed, leading to an anti-diol instead. Therefore, water's presence directly dictates the cis- or syn-outcome.
5. Are the "Woodward Reaction" and "Woodward's Rules" the same concept?
No, these are two completely different concepts in chemistry, although both are named after the Nobel laureate Robert Burns Woodward.
- The Woodward Reaction is a synthetic organic reaction used to create syn-diols from alkenes.
- Woodward's Rules (or Woodward-Fieser Rules) are a set of empirical rules used in spectroscopy to predict the wavelength of maximum UV absorption (λmax) for conjugated organic compounds. They are used for structural analysis, not synthesis.
6. What is the specific role of silver acetate in the Woodward reaction mechanism?
Silver acetate (CH₃COOAg) serves two essential functions in the mechanism:
- It activates iodine by reacting with it to form an electrophilic iodinating agent, acetyl hypoiodite (CH₃COOI), which adds across the alkene's double bond.
- The silver ion (Ag⁺) assists in forming the key cyclic iodonium ion intermediate by precipitating out as silver iodide (AgI), which facilitates the subsequent nucleophilic attack that drives the reaction forward.
7. What are the typical limitations or disadvantages of using the Woodward reaction?
While effective, the Woodward reaction has some practical limitations:
- Cost: The reaction requires a stoichiometric amount of expensive silver salts, making it less economical for large-scale synthesis compared to catalytic methods.
- Steric Hindrance: It may be inefficient for highly substituted or sterically crowded alkenes, which can react very slowly or not at all.
- Functional Group Intolerance: The oxidative conditions can interfere with other sensitive functional groups that may be present in the starting material.
