Wittig Reaction - Kemicalinfo

Introduction: Wittig reaction

The Wittig reaction, named after its discoverer Georg Wittig, is a powerful tool for the synthesis of alkenes from aldehydes and ketones. Organic chemists widely use this reaction, considering it one of the most important methods for forming carbon-carbon double bonds.

The reaction involves the reaction of a phosphorus ylide with a carbonyl compound (aldehyde or ketone) to form an alkene and a phosphine oxide. Typically, one carries out the reaction in the presence of a strong base such as potassium tert-butoxide or sodium hydride.

The choice of the phosphorus ylide controls the selectivity of the Wittig reaction. The ylide can be stabilized or destabilized, which affects the reaction outcome. For example, a stabilized ylide will preferentially form a cis-alkene, while a destabilized ylide will preferentially form a trans-alkene.

Reaction equation

The general reaction equation for the Wittig reaction is:

R2CH=O + R1CH2-PPh3 → R2CH=CHR1 + O=PPh3

In this equation, R1 & R2 represent an alkyl or aryl group, and PPh3 represents a triphenylphosphine group. The reaction involves the formation of a phosphorus ylide intermediate, which then reacts with the carbonyl compound to form an alkene and a phosphine oxide byproduct. The reaction is typically carried out in an inert solvent, such as tetrahydrofuran or dichloromethane, and may be catalyzed by a base, such as potassium t-butoxide or sodium hydride.

Mechanism of the Wittig reaction

The mechanism of the Wittig reaction, a powerful method for the synthesis of alkenes from aldehydes and ketones, involves several key steps.

Step 1: Formation of the Phosphorus Ylide The reaction begins with the formation of the phosphorus ylide, which is achieved by reacting a phosphine with a strong base such as potassium tert-butoxide or sodium hydride. This step results in the formation of a negatively charged carbon attached to a positively charged phosphorus.

Step 2: Reaction with the Carbonyl Compound The phosphorus ylide then reacts with the carbonyl compound (aldehyde or ketone) to form a betaine intermediate. In this step, the negatively charged carbon attacks the positively charged carbon of the carbonyl, resulting in the formation of a new carbon-carbon bond.

Step 3: Formation of the Oxaphosphetane Intermediate The betaine intermediate then undergoes a [2+2] cycloaddition reaction to form an oxaphosphetane intermediate. This intermediate contains a four-membered ring in which the phosphorus, carbon, and two oxygen atoms are part of the ring.

Step 4: Collapse of the Oxaphosphetane Intermediate Finally, the oxaphosphetane intermediate collapses to form the desired alkene and phosphine oxide. This step involves the breaking of the four-membered ring, resulting in the formation of a carbon-carbon double bond and a phosphine oxide.

Factors Affecting Wittig reaction

Several factors can affect the outcome of the Wittig reaction, a powerful method for the synthesis of alkenes from aldehydes and ketones. These factors include:

Choice of Phosphorus Ylide The selectivity of the Wittig reaction can be controlled by the choice of phosphorus ylide. Stabilized ylides tend to form cis-alkenes, while destabilized ylides tend to form trans-alkenes.
Steric Hindrance Steric hindrance can affect the reaction outcome. Bulky substituents on the carbonyl compound or the phosphorus ylide can hinder the reaction and reduce its efficiency.
Reaction Conditions The choice of reaction conditions can also affect the outcome of the Wittig reaction. For example, the reaction may not proceed well in the presence of water or other protic solvents.
Substrate Reactivity The reactivity of the substrate can also affect the outcome of the reaction. For example, substrates with electron-withdrawing groups on the carbonyl may not react well with some phosphorus ylides.
Side Reactions The Wittig reaction may also be prone to side reactions such as over-reduction, which can reduce the yield of the desired product.

Applications of Wittig reaction

The Wittig reaction, a powerful method for the synthesis of alkenes from aldehydes and ketones, has many applications in organic chemistry. Some of the key applications include:

The Wittig reaction finds extensive use in the synthesis of natural products, such as steroids, terpenes, and alkaloids.
Pharmaceutical synthesis employs the Wittig reaction for the creation of various drugs, including anti-cancer, anti-inflammatory, and anti-viral medications.
The Wittig reaction proves useful in polymer synthesis, particularly in the creation of polymers with conjugated double bonds.
In materials science, researchers use this reaction to synthesize various materials, including organic semiconductors, liquid crystals, and light-emitting diodes.
Bioconjugation is another area where this reaction finds application, particularly in the conjugation of biomolecules like proteins and peptides with other molecules.

History of Wittig reaction

The Wittig reaction, named after its discoverer Georg Wittig, is a powerful method for the synthesis of alkenes from aldehydes and ketones. The reaction was first reported in 1954, and Wittig was awarded the Nobel Prize in Chemistry in 1979 for his discovery.

Wittig was born in Berlin in 1897 and studied chemistry at the Technical University of Berlin. After completing his PhD in 1926, he worked as an assistant to the famous chemist Karl Ziegler. In 1932, he became a professor at the University of Freiburg and later at the University of Tübingen.

Wittig’s discovery of the reaction that bears his name came during his time at Tübingen. In 1954, he reported the synthesis of alkenes from aldehydes and ketones using a phosphorus ylide. He had been studying the reactions of phosphorous compounds with organic compounds before making this discovery. The reaction quickly gained widespread use due to its high selectivity and efficiency for the synthesis of alkenes.

Georg Wittig’s discovery of the reaction had a significant impact on the field of organic chemistry. The reaction quickly became widely used due to its high selectivity and efficiency for the synthesis of alkenes. Organic chemists continue to use the Wittig reaction frequently today.

Limitations of Wittig reaction

While the Wittig reaction is a powerful method for the synthesis of alkenes, it does have some limitations that should be considered. Some of the key limitations include:

Substrate Reactivity The reactivity of the substrate can affect the outcome of the reaction. For example, substrates with electron-withdrawing groups on the carbonyl may not react well with some phosphorus ylides.
Stereoselectivity While the Wittig reaction is highly stereoselective, it may not always produce the desired stereoisomer. In some cases, the reaction may produce a mixture of cis and trans isomers, which can be difficult to separate.
Over-reduction The reaction may be prone to over-reduction, which can reduce the yield of the desired product.
Reaction Conditions The choice of reaction conditions can also affect the outcome of the Wittig reaction. For example, the reaction may not proceed well in the presence of water or other protic solvents.
Bulky Substituents Bulky substituents on the carbonyl compound or the phosphorus ylide can hinder the reaction and reduce its efficiency.

Overall, while the Wittig reaction is a powerful tool for the synthesis of alkenes, it is important to carefully consider its limitations in order to optimize the reaction and achieve the desired results. Other methods, such as olefin metathesis or hydrogenation, may be more suitable for certain substrates or reaction conditions.