Alexander Davies Introduction Alkenes are important initial building blocks in many organic synthesis routes, as shown by Scheme 1. Examples of one-step reactions from an alkene starting material.
Classical mechanism[ edit ] The steric bulk of the ylide 1 influences the stereochemical outcome of nucleophilic addition to give a predominance Wittig reaction the betaine 3 cf.
Carbon-carbon bond rotation gives the betaine 4, which then forms the oxaphosphetane 5. Elimination gives the desired Z-alkene 7 and triphenylphosphine oxide 6. With simple Wittig reagents, the first step occurs easily with both aldehydes and ketonesand the decomposition of the betaine to form 5 is the rate-determining step.
However, with stabilised ylides where R1 stabilises the negative charge the first step is the slowest step, so the overall rate of alkene formation decreases and a bigger proportion of the alkene product is the E-isomer.
This also explains why stabilised reagents fail to react well with sterically hindered ketones. Mechanism[ edit ] Mechanistic studies have focused on unstabilized ylides, because the intermediates can be followed by NMR spectroscopy.
The existence and interconversion of the betaine 3a and 3b is subject of ongoing research. The stereochemistry of the product 5 is due to the addition of the ylide 1 to the carbonyl 2 and to the equilibration of the intermediates.
However, certain reactants do not follow this simple pattern. Lithium salts can also exert a profound effect on the stereochemical outcome. Evidence suggests that the Wittig reaction of unbranched aldehydes under lithium-salt-free conditions do not equilibrate and are therefore under kinetic reaction control.
The alkylphosphonium salt is deprotonated with a strong base such as n-butyllithium: The ylide form is a significant contributor, and the carbon atom is nucleophilic.
Reactivity[ edit ] Simple phosphoranes typically hydrolyze and oxidize readily. They are therefore prepared using air-free techniques. Phosphoranes are more air-stable when they contain an electron withdrawing group attached to the carbon.
These ylides are sufficiently stable to be sold commercially. The resulting phosphoranes are however less reactive than ylides lacking EWGs. For example they usually fail to react with ketones, necessitating the use of the Horner—Wadsworth—Emmons reaction as an alternative.
Such stabilized ylides usually give rise to an E-alkene product when they react, rather than the more usual Z-alkene. Although phosphoranes are "electron-rich", they are often susceptible to deprotonation. The Wittig reagent can generally tolerate carbonyl compounds containing several kinds of functional groups such as OHORaromatic nitro and even ester groups[ citation needed ].
There can be a problem with sterically hindered ketones, where the reaction may be slow and give poor yields, particularly with stabilized ylides, and in such cases the Horner—Wadsworth—Emmons HWE reaction using phosphonate esters is preferred.
Another reported limitation is the often labile nature of aldehydes which can oxidize, polymerize or decompose. In a so-called Tandem Oxidation-Wittig Process the aldehyde is formed in situ by oxidation of the corresponding alcohol.
Quaternization of triphenylphosphine with most secondary halides is inefficient. For this reason, Wittig reagents are rarely used to prepare tetrasubstituted alkenes. However the Wittig reagent can tolerate many other variants. It may contain alkenes and aromatic ringsand it is compatible with ethers and even ester groups.The Wittig reaction provides a path from aldehydes and ketones to alkenes, and consequently is a valuable tool in organic synthesis.
For example, the Wittig reaction will convert an α,β-unsaturated ketone to a conjugated alkene. The reactions of α-phosphorus nucleophiles with carbonyl compounds are reliable methods for the synthesis of olefins. There are two principal variants: the Wittig Reaction, which uses phosphonium ylids as nucleophiles, and the Horner-Wadsworth-Emmons reaction, which uses metalated phosphonates.
The Wittig Reaction allows the preparation of an alkene by the reaction of an aldehyde or ketone with the ylide generated from a phosphonium salt.
The geometry of the resulting alkene depends on the reactivity of the ylide. If R'' is Ph or R is an electron withdrawing group, then the ylide is stabilized and is not as reactive as when R'' and R. The Wittig reaction is an important method for the formation of alkenes. The double bond forms specifically at the location of the original aldehyde or ketone.
Ylides are neutral molecules but have +ve and -ve centers on adjacent atoms that are connected by a s bond. 1 Introduction The Wittig reaction, discovered in by Georg Wittig, is one of the most common tech-niques used for the stereoselective preparation of alkenes.
The Wittig reaction provides a path from aldehydes and ketones to alkenes, and consequently is a valuable tool in organic synthesis. For example, the Wittig reaction will convert an α,β-unsaturated ketone to a conjugated alkene.