Wittig Reaction: Videos & Practice Problems

The Wittig reaction is a crucial method for forming carbon-carbon bonds between aldehydes or ketones and ylides, resulting in regiospecific alkenes. The mechanism involves creating an ylide from an alkyl halide and triphenylphosphine, followed by nucleophilic addition to a carbonyl. This process generates a betaine intermediate, which transforms into an oxaphosphetane before yielding the desired alkene product. Notably, the reaction is regioselective but not stereospecific, allowing for the formation of both E and Z isomers when applicable.

Box-Out Method and Full-Mechanism

The Wittig reaction is a crucial method in organic chemistry for forming carbon-carbon double bonds, specifically alkenes, from aldehydes and ketones. This reaction is notable for its regiospecificity, meaning it allows chemists to control the placement of substituents on the resulting alkene. The process involves the reaction of a carbonyl compound with a special type of compound known as an ylide.

An ylide is formed from an alkyl halide and triphenylphosphine through an SN2 reaction, where the alkyl halide acts as a leaving group. The triphenylphosphine, which has a nucleophilic lone pair, attacks the alkyl halide, resulting in the formation of a positively charged phosphorus species. This species is then deprotonated using a strong base, typically butyllithium, to create the ylide, characterized by adjacent positive and negative charges.

When the ylide reacts with a carbonyl compound, a nucleophilic addition occurs. The negatively charged carbon of the ylide attacks the electrophilic carbon of the carbonyl, leading to the formation of a tetrahedral intermediate known as a betaine. This intermediate can undergo further transformation to yield an oxaphosphetane, a four-membered ring structure. The final step involves the elimination of the phosphorus-containing byproduct and the formation of the desired alkene product.

To simplify the process of predicting the product of a Wittig reaction without delving into the detailed mechanism, the box-out method can be employed. This method involves positioning the ylide and carbonyl so that the phosphorus and oxygen are nearly touching, drawing a box around them, and visualizing the resulting alkene. This approach allows for quick identification of the product without extensive memorization of the reaction mechanism.

It is important to note that while the Wittig reaction is regiospecific, it is not stereospecific. This means that if multiple stereoisomers can be formed, both E and Z configurations may be produced, depending on the substituents involved. Understanding these concepts is essential for mastering the Wittig reaction and its applications in organic synthesis.

Determine the carbonyl and ylide that formed the following product.

• A.
• B.
• C.
• D.

Answer: (C)

Here’s what students ask on this topic:

What is the Wittig reaction and why is it important in organic chemistry?

The Wittig reaction is a chemical reaction used to form carbon-carbon double bonds (alkenes) by reacting an aldehyde or ketone with a phosphonium ylide. This reaction is crucial in organic chemistry because it allows for the regiospecific formation of alkenes, meaning you can control the position of substituents on the double bond. This is particularly useful for synthesizing complex molecules with precise structural requirements. The reaction is named after Georg Wittig, who was awarded the Nobel Prize in Chemistry in 1979 for this discovery.

How is an ylide formed in the Wittig reaction?

An ylide is formed in the Wittig reaction by reacting an alkyl halide with triphenylphosphine. The triphenylphosphine performs an SN2 nucleophilic attack on the alkyl halide, displacing the halide ion and forming a phosphonium salt. This intermediate is then deprotonated by a strong base, commonly butyllithium (BuLi), to generate the ylide. The ylide has a positively charged phosphorus atom adjacent to a negatively charged carbon atom, which is crucial for the subsequent steps in the Wittig reaction.

What is the mechanism of the Wittig reaction?

The mechanism of the Wittig reaction involves several steps. First, an ylide is formed from an alkyl halide and triphenylphosphine. The ylide then reacts with a carbonyl compound (aldehyde or ketone) in a nucleophilic addition, forming a betaine intermediate. This intermediate rearranges to form an oxaphosphetane, a four-membered ring structure. Finally, the oxaphosphetane decomposes to yield the desired alkene and a byproduct, typically triphenylphosphine oxide. The overall process is regiospecific but not stereospecific, meaning it can produce both E and Z isomers of the alkene.

What are the limitations of the Wittig reaction?

While the Wittig reaction is highly useful, it has some limitations. One major limitation is its lack of stereospecificity, meaning it can produce both E and Z isomers of the alkene product. Additionally, the reaction is sensitive to the steric hindrance of the starting materials; it works best with primary and secondary alkyl halides and is less effective with tertiary alkyl halides. The reaction also requires the use of strong bases, which can limit its applicability with base-sensitive substrates. Despite these limitations, the Wittig reaction remains a powerful tool for synthesizing alkenes.

What is the difference between a betaine and an oxaphosphetane in the Wittig reaction?

In the Wittig reaction, a betaine is an intermediate formed after the nucleophilic addition of the ylide to the carbonyl compound. It features non-adjacent positive and negative charges. The betaine then rearranges to form an oxaphosphetane, a four-membered ring structure containing oxygen and phosphorus. The oxaphosphetane is a key intermediate that eventually decomposes to yield the final alkene product and triphenylphosphine oxide. Understanding these intermediates is crucial for grasping the full mechanism of the Wittig reaction.