Wittig Reaction, Example, Mechanism, and Stereochemistry.

Wittig reaction is an important method for the synthesis of the desired alkene. In this reaction, carbonyl compounds (aldehyde or ketone) are treated with phosphorus ylides to form alkenes and triphenylphosphine oxide (as a by-product). Phosphorus ylide is also known as a Wittig reagent. E and Z alkenes are formed as a product of the Wittig reaction.

example of wittig reaction

Wittig’s reaction is named after its discoverer Georg Wittig. He was awarded with the Noble prize in 1979 for this discovery. This is a very valuable method for the synthesis of an alkene by using carbonyl compounds and Wittig reagent. In this reaction, carbonyl compounds are converted to alkenes when treated with ylids. The stereochemistry of this reaction depends upon the reactivity of ylide.

What is a ylide/phosphorus ylide?

Ylide is a neutral dipolar molecule having a negative charge and a positive charge on adjacent atoms. The term ylide is also spelled as ylid. In the Wittig reaction phosphorus ylides are used as a Wittig reagent. Phosphorus ylid contains a negatively charged carbon atom adjacent to a positively charged phosphorus atom. These are also named as phosphoranes.

 

Structure of Ylide/Ylid

structure of phosphorus ylide

Formation of phosphorus Ylide(Wittig reagent)

can be easily prepared by reacting triphenylphosphine with primary or secondary alkyl halides. The synthesis of phosphorus ylide takes place in two steps.

Step 1 (Nucleophilic substitution reaction)

The first step of ylide formation is an SN2-type reaction. Triphenylphosphine is an excellent nucleophile and a weak base. Here alkyl halide act as a substrate. We can use primary o secondary alkyl halide for this reaction because alkyl halide must have a hydrogen atom. This hydrogen is necessary for deprotonation in the second step.

step one of ylide formation

In the first step, triphenylphosphine reacts with alkyl halides and displaces halide ions from alkyl halides. This results in the formation of phosphonium salt. This step is facilitated by microwave irradiation.

Step 2 (Deprotonation)

The second step of ylid formation is the acid-base reaction. In this step, phosphonium salts are treated with strong bases like butyl lithium, sodium amide, sodium hydride, phenyl lithium, or sodium alkoxides. These remove a proton from the carbon atom that is attached to the phosphorus. This converts phosphonium salt to phosphorus ylids. This can be represented by a hybrid of two resonating structures.

step two of ylide formation

Mechanism of Wittig reaction

Formation of a phosphorus ylide:


step one of wittig reaction mechanism
The first step is the cycloaddition reaction. In this step, carbonyl compounds react with phosphorus ylide and form a four-member ring known as oxaphosphetane. In some cases,(E-selective Reactions) during the first step, an intermediate named betaine is formed but not in all cases. In this step, two new stereocenters are formed. There is the possibility of two stereoisomers.

 

step two of wittig reaction mechanism

As we know that smaller rings are unstable due to angle strain. Similarly, oxaphosphetane is unstable and it undergoes an elimination reaction. Their ring collapses to form an alkene as a major product and phosphine oxide as a by-product. two double bonds. P=O is a very stable and strongest double bond. It is the driving force of Wittig’s reaction.

Stereochemistry of Wittig reaction

Wittig reaction is a stereoselective reaction. It results in the formation of a mixture of E/Z isomers of alkene. One of the isomers formed in excess. Some of the Wittig reactions are Z selectivity whereas others are E selective reactions. In the Z selective reaction Z isomer form in excess whereas in E selective reaction E isomer forms in excess.

z- selective wittig reaction stereochemistry of wittig reaction

e-selective wittig reaction

The stereochemistry of the Wittig reaction depends upon the stability of ylids. This stability depends upon the nature of the substituent on the carbon atom. If electron-withdrawing groups are adjacent to the carbon atom they will stabilize the carbanion effectively along with the phosphorus atom.

stabilized and unstabilized ylides

If electron donating groups are adjacent to the carbanion they will not able to stabilize the ylide. With the stable ylide E, selective Wittig reaction takes place whereas, with unstabilized ylide Z, selective Wittig reaction will take place.

Modification of Wittig reaction(Honer Wittig Reaction)

Wittig reaction is modified to get E isomer selectively. The modified reaction of Wittig is named as Honer Wadsworth Emmons reaction. In this reaction, phosphonates esters are used instead of phosphonium slat. These esters are deprotonated by a strong base to form enolate-type anions. When these are treated with carbonyl compounds they give E alkenes.

wittig honor reaction

Advantages of Wittig reaction

  • This is a very simple and quick reaction.
  • We can synthesize desired alkenes by using this reaction.
  • This reaction is applicable to a wide variety of compounds.
  • Similarly, the position of the double bond can be fixed by using a Wittig reaction.
  • We can adjust the position of the double bond as required.
  • The stereochemistry of the product can be easily predicted.
  • With little modification, we can produce a selective product in excess.
  • This reaction is also used for the synthesis of natural products like 𝛃-Carotene, Vitamin A, etc.

Limitations of Wittig reaction

  • A mixture of E/Z isomers is formed.
  • Aldehydes may decompose or undergo polymerization.
  • Similarly, these compounds may oxidize.
  • Separation of phosphine oxide is difficult.
  • In Z selective Wittig reaction produce less yield because of unstable product.

Concepts Berg

Why E isomer is more stable than the Z isomer?

E isomer is more stable than Z isomer because in z isomer has steric crowding due to bulky groups being present on the same side.

Or

Z isomer is less stable than E isomer because they have great repulsive forces due to steric hindrance.

What is meant by ylides?

Ylide is a dipolar neutral molecule having positive and negative charges on adjacent atoms.

Differentiate between stabilized and unstabilized ylide.

Comparison Stabilized ylides Unstabilized ylides
Functional groupElectron withdrawing adjacent to a carbanionElectron donating group adjacent to a carbanion
reactivityLess reactiveMore reactive
Conjugation Presentabsent
Product E isomerZ isomer
Delocalization of electronyesNo
First stepReversibleirreversible
Example structure of stabilized ylidestructure of unstablized ylide

When does E selective reaction take place?

When we use stabilized Wittig reagent then E selective reaction takes place.

When does Z selective Wittig reaction take place?

When we use unstabilized ylides then Z selective reaction takes place.

What does E selective and Z selective reaction mean?

E selective reaction involves the formation of E isomer in excess whereas in Z selective reactions Z isomer forms in excess.

What makes ylides more stable?

Conjugation or delocalization of negative charge makes ylides more stable.

What is the advantage of the use of phosphonate esters?

Advantages of phosphonate ester

These are cheaper than phosphonium salt.

They provide more selectivity in a chemical reaction.

E isomer is formed in greater excess.

Phosphate esters are produced as by-products.

These esters are easy to separate because they are soluble in water.

Reference:

  • 10th edition of Organic Chemistry by T.W Graham Solomons and Craig B. Fryhle.
  • 2nd edition of Organic Chemistry by Jonathan Clayden, Nick Greeves, and Stuart Warren.
  • 7th edition of March’s Advanced Organic Chemistry by Micheal B. Smith.

Was this article helpful?