Woodward Reaction

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:

  1. First, Iodine and alkene react with each other and form a cyclic intermediate.

  2. Again, the iodonium cyclic intermediate and acetate ion start a reaction in SN2 fashion and form a ring compound of five members.

  3. Hydrolysis reaction opens the five-membered rings.

  4. 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.

FAQ (Frequently Asked Questions)

Q1. What are Woodward and Prevost Reactions?

Ans. Both Woodward and Prevost reactions relate to the addition of iodine carboxylate to an alkene. They represent the reaction of alkenes to iodine and silver salt. In the Prevost reaction, every reaction takes place in dry conditions. At first, the trans-iodocarboxylate reacts and forms into a cyclic iodonium ion. Which then undergoes internal displacement to form an intermediate acylium ion. Due to the retention of configuration, a diester is formed. When hydrolysis of the diester takes place, we get trans-glycol. The Woodward reaction needs water to carry out the reactions. On subsequent hydrolysis, water is used to intercept the intermediate to give cis-hydroxy ester and a cis-glycol.

Q2. Compare Woodward Hydroxylation with Osmium Tetroxide Oxidation.

Ans. Both the methods are complementary to each other while giving the same end product, i.e. cis-glycol. But both the end products show opposite diastereoselective nature. Cis-glycol from Osmium Tetroxide Oxidation is sterically less hindered compared to what we get from Woodward method. In the following picture, we have considered a rigid cyclohexene compound, and in both the procedures, the first ring intermediate is formed on a less hindered alpha side. However, there is another cyclic intermediate in Woodward method, and as a result, we get reversed stereochemistry in the end product.

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The image shows the comparison of Woodward Hydroxylation with Osmium Tetroxide Oxidation.