The formation of carbon-carbon double bonds from the reaction of active carbonyl compounds and phosphorous ylides ("phosphoranes") is known as the Wittig reaction. The reaction is named after Georg Wittig who first reported this reaction in 1953 in collaboration with Georg Geissler. It is worthy of note that work had been conducted on phosphorous ylides as early as 1919 by Staudinger, Meyer and Marvel.
This is a classical organic reaction which is heavily employed today as a way of creating olefins (unsaturated hydrocarbons). There are many modifications and similar reactions two the Wittig, which emphasise how important this reaction is to the modern organic chemist. Two prominent examples (namely the Schlosser modification, and the Horner-Wadsworth-Emmons modification) are given on their own pages within this resource.
Scheme W1: The Wittig reaction
The first step of the mechanism is the formation of the phosphorous ylide. This is a simple nucleophilic attack, which is propagated by the removal of the α-proton with a base. This sets up the electronic resonance between (i) and (ii).
Scheme W2: Formation of the phosphorous ylide
Scheme W3: Attack of the ylide on a ketone to afford an alkene
There are three classes of ylide, and they lend themselves to different isomer formations:
- "non-stabilized ylides" (if R1 is aryl, and R2 and R3 are alkyl, or H
- "semi-stabilised ylides" (if R1 is aryl, and R2 and R3 are aryl, alkenyl, benzyl, or allyl
- "stabilised ylides" (if R1 is aryl, and R2 and R3 are -CO2R, -SO2R, -CN or -COR
Non-stabilised ylides, under salt free conditions in polar aprotic solvents with aldehydes give high (Z)-selectivity (shown below).
Stabilised ylides give good (E)-selectivity when reacting under the same conditions.
Semi-stabilised ylides give generally poor selectivity.
Scheme W4 shows the reaction of an ylide with an aldehyde. The reaction starts with the formation of the carbon-carbon bond (top centre), and the next step is critical to the selectivity: transition species (iii) (the trans-betaine) has a steric problem whereby functional group R3 may interact with the phosphorous containing unit. The formation of (iv) (the cis-betaine) has no such steric problem, and thus forms faster than (iii). This first step is the slowest step of the reaction, and after the rearrangement of the oxygen negative charge and formation of the oxygen-phosphorous bond, gives the respective oxaphosphetane. The oxaphosphetane eliminates the phosphorous containing group to give the alkene. The isomer yeilded is thus dependant on the ease of formation of the transition state compounds. In the case that we reacted the ylide with a ketone, then the product would form the betaine with the least steric hindrance. Using this knowledge, and that of the nature of ylides it is possible to engineer reagents and conditions with which to provide some degree of selectivity towards a desired product.
Scheme W4: Selectivity in the Witting reaction.
- Aldehydes react much faster than ketones.
- Phosphorous ylides are oxygen and moisture sensitive and so are usually formed in situ, however they can, with care, be pre-formed
- Suitable solvents are polar and aprotic. Examples commonly used are ethers, such as THF, Et2O, and DME.
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