C=C bond generation in organic chemistry

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2. WITTIG REACTION
Dr. Shahid Rasool Wittig reaction CHEM5128
Advanced Named Reactions
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3. Key Concepts
• Introduction to Wittig reaction
• Discussion of reacting species, bases
• Mechanism of reaction
• Explanation of mechanism step by step
• Synthetic applications
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4. Wittig Reaction:
• In 1954, G. Wittig introduced the reaction
• Triphenylphosphane (triphenylphosphine) reacts alkyl halides to
produce phosphonium salt
• Phosphonium salt is converted to phosphorane by a base
• Phosphorane (phosphorus ylide) reacts aldehydes or ketones to
produce alkene
• A way to prepare olefins from aldehydes or ketones
• Overall reaction,

5. Phosphane, Phosphonium salt & Phosphoranes:
• Organo-phosphorus compounds
• Phosphane or Phosphine is normally bonded phosphorus (3 bonds)
• Phosphonium salt is phosphorus with 4 bonds
• Phosphorane is phosphorus with 5 bonds
H P
H
H
H R P
H
R
R
Phosphonium Protonated organophosphine
R P
R
R
R
Tetraorganophosphonium
PCl3 + 3 PhMgCl → PPh3 + 3 MgCl2
PCl3 + 3 PhCl + 6 Na → PPh3 + 6 NaCl
PCl3 + 3 PhLi → PPh3 + 3 LiCl
R P
R
R
R R P
R
R
R
R

6. Phosphoranes or Phosphorus ylide:
• Phosphoranes are also called phosphorus ylide or phosphonium
ylide
• Ylide is a compound having an uncharged molecule containing a
negatively charged carbon atom directly bonded to a positively
charged atom of sulphur, phosphorus, nitrogen, or another element
• Ylide is a species with opposite formal charges on adjacent atoms
• Carbon bears a nucleophillic character which attacks on carbonyl.
• Ylides have been known for sulphur, phosphorus, nitrogen and
oxygen
Ylene form or

7. Types of Phosphorus ylide:
Unstabilized phosphorus ylide
• These have either H or alkyl groups connected to the C atom.
• Alkyl groups are EDG and destabilize charge separation.
• Ylene form predominates and reactions occur through it.
Stabilized phosphorus ylide
• The subtituents on the C atom must be ones that can stabilize the
negative charge by delocalization.
• Since charge stabilization is achieved through resonance
delocalization, the ylide form predominates.
Ylene form
Ylide form

8. Alkylating agents and bases:
• Alkyl halides or Alkyl sulfonates can be used.
• Nature of alkyl group results into stabilized or unstabilized
phosphorus ylide.
• Unstabilized phosphorus ylide reacts through its ylene form and
produces Z-alkene predominantly.
• Stabilized phosphorus ylide reacts through its ylide form and
produces E-alkene predominantly.
• Different bases used for deprotonation include alkyl lithium (RLi),
NaH, LiH, NaNH2 etc
R C
R
R
X R S
O
O
O
Alkyl halides Alkyl sulfonate

9. Complete Mechanism:

10. Step-1, Formation of phosphonium salt:
• Triphenylphosphine reacts with alkyl halide through SN2
mechanism.
• Triphenylphosphine acts as a nucleophile due to lone pair of
phosphorus.
• Nucleophilicity of phosphorus is greater than that of nitrogen due
to large size.
• The α-carbon of alkyl halide act as an electrophilic center.
• Why there is substitution and not elimination? (PPh3 is a strong
nucleophile and not a strong base)

11. Step-2, Ylide formation:
• Deprotonation of phosphonium salt results into ylide formation.
• Strong base can be used to remove proton.
• The α-hydrogen of phosphonium salt is removed by base.
• Resulting product has two forms i.e. Ylene form or Ylide form
• Why is it easy to remove proton from a C-H bond?
• Which form is dominating? Ylene form or Ylide form?

12. Step-2, Ylide formation:
Preparation of Unstabilized Phosphorus Ylides
• Alkyl groups are EDG and destabilize charge separation.
• Ylene form predominates and reactions occur through it.
• Phosphonium group is EWG so C-H bond is acidic.
(Lithium diisopropylamide)

13. Step-2, Ylide formation:
Preparation of Stabilized Phosphorus Ylides
• EWG stabilizes the charge through resonance delocalization
• Ylide form predominates and reactions occur through it.
• Two EWG, so C-H bond is acidic.

14. Step-3, Olefin formation:
• The ylide reacts with aldehyde or ketone through a cyclic
mechanism to form olefin.
• The –vely charged carbon of ylide acts as nucleophile.
• The step 1 and step 2 may occur simultaneously.
• The byproduct along with alkene is Ph3P=O, also called
triphenyl(oxo)phosphorane or triphenylphosphine oxide.

15. Stereochemistry:
• Unstabilized phosphorus ylide reacts through its ylene form and
produces Z-alkene predominantly.
• Stabilized phosphorus ylide reacts through its ylide form and
produces E-alkene predominantly.
Schlosser Modification:
• Reaction proceeds mainly via erythro betaine intermediate-
produces Z-alkene. (erythro means identical group on same side)
• erythro betaine into threo by phenyllithium at low temperature-
produces E-alkene. (threo means identical group on opposite side)

16. Stereochemistry (Schlosser Modification):

17. Stereochemistry:
• Unstabilized phosphorus ylide reacts through its ylene form and
produces Z-alkene predominantly.

18. Stereochemistry:
• Stabilized phosphorus ylide reacts through its ylide form and
produces E-alkene predominantly.

19. Advantages of Wittig Reactions:
• Alkenes can be synthesized from aldehydes or ketones
• Tolerance of carbonyl compounds with many different kinds of
functional groups like OH group, OR group, etc. by the Wittig
reagent.
• The geometry of the double bond can easily be predicted if the
Ylide’s nature is known.
Limitations of Wittig Reactions:
• Both the E and the Z double bond isomers can be formed.
• The reaction speed is very slow when sterically hindered ketones
are used. The yield is also low for these reactions.
• Aldehydes can easily undergo oxidation, decomposition, or even
polymerization.

20. Comparison of HWE and Wittig Reactions:
• HWE uses more nucleophillic and reactive phosphonate-stabilized
carbanions than phosphonium ylide
• Phosphonium ylide bears a neutral form and neutral species are
less reactive than charged species
• HWE byproduct dialkylphosphate salt is easily removed by water
during workup than triphenylphosphine oxide (Wittig reaction)
• HWE produces E-alkenes and Wittig reaction produces Z-alkenes.
RO P
O
OR
CH C
O
OR RO P
O
OR
CH C
O
OR
phosphonate-stabilized carbanions

21. Examples of Wittig Reaction:
Sodium dodecyl
sulfate (SDS)

22. Examples of Wittig Reaction: