Wittig Reaction: Reagent Preparation, Mechanism, Advantages, Limitations

Wittig reaction occurs when Alkenes are generated during a phosphonium reaction with an aldehyde (or ketone). Ylides are compounds that have adjacently positioned covalently bound atoms with opposite charges and full octets. Phosphorus with a positive charge is covalently bonded to carbon with a negative charge in phosphonium ylides. A structure with a double bond between phosphorus and carbon can be used to symbolize them.

Key Terms: Wittig reaction, Synthesis of alkenes, phosphorus ylide, Wittig reagents, aldehyde, ketone, carbon, Phosphorus, octets, phosphonium, ylides

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What is Wittig Reaction?

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When an aldehyde or ketone reacts with phosphonium ylide in the Wittig reaction, alkenes are formed.

Below given is the general Wittig reaction Synthesis of alkenes:

Some of the examples are given below:

The trialkyl or triaryl phosphine oxide is the by-product of the interchange of the doubly bonded carbon part of ylide with carbonyl oxygen.

To understand the mechanism of this reaction, we must first learn more about the phosphonium ylide, also known as the Wittig reagent.

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Phosphonium Ylide (Wittig Reagent)

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Phosphorus atoms, particularly those that are positively charged or that are connected to electronegative substituents, can raise the acidity of protons close to them in the carbon skeleton.

When phosphorus ylide is deprotonated by a fairly strong base, it produces phosphoranes, which are doubly bound.

An SN2 reaction between triphenylphosphine and an alkyl halide with the appropriate amount of carbon atoms produces the phosphonium ylide needed for a specific synthesis.

The ylides are resonance stabilized structures with brilliant colours. On neighboring atoms, it has a positive and negative charge. In most cases, they are not engulfed by the solution in which they are prepared. As a result, during the Wittig reaction, they are created in situ.

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Wittig Reagents Preparation

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Hydrolysis and oxidation of simple phosphoranes are common. As a result, they are prepared without the need for air. Phosphoranes having an electron-withdrawing group linked to the carbon are more air-stable. Ph₃P=CHCO₂R and Ph₃P=CHPh are two examples. These ylides are stable enough to sell commercially.

In most cases, Wittig reagents are made from a phosphonium salt, which is made by quaternizing triphenylphosphine with an alkyl halide. A strong base, such as n-butyllithium, is used to deprotonate the alkyl phosphonium salt:

[Ph₃P +CH₂R]X − + C₄H₉Li → Ph₃P=CHR + LiX + C₄H₁₀

Other strong bases, such as sodium and potassium t-butoxide ( tBuONa, tBuOK), lithium, sodium, and potassium hexamethyldisilazane (LiHMDS, NaHMDS, KHDMS, where HDMS = N(SiMe3 )2, or sodium hydride (NaH), are widely utilized. Even very weak bases like aqueous sodium hydroxide or potassium carbonate can be used to stabilize Wittig reagents containing conjugated electron-withdrawing groups.

When it comes to optimizing a Wittig reaction, finding a good base is frequently a crucial step. Because phosphonium ylides are rarely separated, the deprotonation byproduct(s) basically acts as an additive in the Wittig process.

Methylenetriphenylphosphorane (Ph₃P=CH₂) is one of the most basic ylides.

It also serves as a prelude to more complex Wittig reagents. Substituted phosphonium salts are produced via alkylation of Ph₃P=CH₂ with a primary alkyl halide RCH₂X.

Ph₃P=CH₂ + RCH₂X → Ph₃P + CH₂CH₂R X ^–

Ph₃P=CHCH₂R can be made by deprotonating these salts in the normal way.

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Mechanism of Wittig Reaction

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Following the production of the initial carbon-carbon bond, the Wittig reaction has two intermediates: a dipolar charge-separated molecule known as a betaine and a four-membered heterocyclic structure known as an oxaphosphatane. Exothermic and irreversible cleavage of the oxaphosphatane to alkene and phosphine oxide compounds.

Nucleophilic attack on the carbonyl

The ylide's negatively charged carbon acts as a nucleophile. This carbon then attacks the aldehyde or ketone's carbonyl carbon with a nucleophilic assault. This results in the creation of betaine, a charge-separated (and dipolar) intermediate. Refer to the below reaction:

Nucleophilic attack on the carbonyl

Formation of a 4 membered ring

The betaine intermediate generated in step 1 is now subjected to the production of a new oxygen phosphorus bond, resulting in a four-membered ring structure intermediate. Refer to below reaction:

Formation of a 4 membered ring

Formation of the alkene

The carbon-oxygen and carbon-phosphorus bonds are cleaved in the four-membered ring intermediate. Both bonding electrons are taken by oxygen, which forms a new double bond with phosphorus, which has lost its bonding pair of electrons to the carbon atom. With this electron pair, a new carbon-carbon double bond is created, providing the desired alkene product. Refer below reaction:

Formation of alkene

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Advantages and Limitations of Wittig Reaction

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Advantages

• The Wittig reaction produces alkenes in an irreversible manner.
• The Wittig reaction is one of the most important reactions in organic chemistry since it is both reliable and extensively applicable.

Limitations

• The Wittig reaction progresses mostly through the erythro betaine intermediate, which leads to the Z-alkene. At low temperatures, phenyl lithium can be used to convert erythro betaine to three betaine. The E-alkene is produced as a result of this alteration.
• When sterically hindered ketones are utilized, the reaction speed is extremely slow. These reactions have a low yield as well.
• Aldehydes can be easily oxidized, decomposed, and even polymerized.

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Things to Remember

• This reaction converts aldehyde and ketones' C=O bonds to C=C bonds, and it's the most common way to make alkenes with specific substituent geometries.
• It makes use of phosphorus ylide, a chemical species in which the phosphorus has a positive charge while the surrounding carbon has a negative charge.
• The principal disadvantage of the Wittig reaction is the difficulty in removing the phosphine oxide side product on occasion.
• The Wittig-Horner reaction (also known as the Horner-WadsworthEmmons reaction) is a better reaction that uses phosphites instead of phosphine’s and creates a highly polar/water-soluble phosphorus side product that is easily removed
• It’s a carbon-carbon bonding reaction that permits the carbon chain to be extended.
• The constituents (carbonyls and ylides) are readily available and/or simple to synthesize from readily available precursors.
• The alkenes that result can then be converted into a wide range of functional groups.

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