C=C Formation

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Chapter: Organic Chemistry : Carbon-Carbon Bond Formation Between Carbon Nucleophiles and Carbon Electrophiles

In addition to connecting skeletal fragments by formation of carbon–carbon single bonds, it is also possible to utilize reactions which give carbon–carbon double bonds to assemble carbon skeletons.


In addition to connecting skeletal fragments by formation of carbon–carbon single bonds, it is also possible to utilize reactions which give carbon–carbon double bonds to assemble carbon skeletons. It should be recognized that while the final products of such reactions contain a carbon–carbon double bond, they are gen-erally sequential processes in which a single carbon–carbon bond is formed first and the π bond is formed in a subsequent elimination step.

An elementary example of this process is the reaction of an organometallic reactant with a ketone (or aldehyde) followed by dehydration of the resulting alcohol to the olefin. This is truly a sequential process in that the product alco-hol is dehydrated in a second, independent reaction step. It suffers as a useful synthetic method because regioisomers are often formed in the elimination step.

Alternatively it is possible to have both steps, addition and elimination, occur spontaneously if appropriate reagents are employed. There are two common strategies in use: the Wittig reaction and the Wittig–Horner reaction. The Wittig olefination uses a phosphorus-stabilized carbanion (ylid) as a nucleophile and a carbonyl compound as an electrophile. Typically the ylid is generated in situ from a triphenylphosphonium salt and a strong base such as LDA or an alkyl lithium.

The ylid is a neutral compound which is resonance stabilized by phosphorus. The phosphorus atom, being a second-row element, has unfilled d orbitals in the valence shell that can accept electrons from carbon. Consequently a major resonance contributor is a structure without formal charges which has a car-bon–phosphorus double bond. Nevertheless in the resonance hybrid the carbon atom next to the phosphorus is electron rich and is a good carbon nucleophile which can add to carbonyl groups to form new carbon–carbon bonds. The cyclic intermediate (oxaphosphetane) spontaneously loses triphenylphosphine oxide at room temperature to give an olefin.

In sum, a new olefinic link is produced, but by an addition–elimination sequence. In this reaction a stronger C–O double bond in the starting material is replaced by a weaker C–C double bond in the product. The thermodynamic driving force for the reaction is the formation of the P–O bond, which is very strong.

The Wittig reaction is a very important method for olefin formation. The stereochemistry about the new carbon–carbon double bond is the Z (or less stable) isomer. This unusual stereoselectivity indicates that product formation is dominated by kinetic control during formation of the oxaphosphetane.

By adding a strong base to the cold solution of the oxaphosphetane before it eliminates, the oxaphosphetane equilibrates to the more stable anti isomer and the E olefin is produced upon elimination. This so-called Schlosser modification in conjunction with the normal Wittig reaction enables either the Z or E isomer of the olefin to be prepared selectively.

The Wittig–Horner reaction is the Wittig process applied to carbonyl-activated ylids and uses trimethylphosphite as the phosphorous reagent. Reaction with a bromoester gives a phosphate intermediate. Deprotonation with a base such as sodium hydride and addition of an aldehyde or ketone gives, after elimination of a phosphonate, an α,β-unsaturated ester. In this case the intermediate betaine is acidic and undergoes equilibration prior to elimination so that only the more stable E regioisomer is produced.

A recent alternative to the Wittig reaction uses silicon as the atom which promotes oxygen loss. This reaction, called Peterson olefination, uses an α-silyl anion as the carbon nucleophile and a carbonyl compound (aldehyde or ketone) is the electrophile. Thus ethyl α-trimethylsilylacetate can be converted to an enolate and reacts with an aldehyde to give an α,β-unsaturated ester. The driving force for elimination is the formation of an extremely strong silicon–oxygen bond, which converts the oxygen atom into a much better silyloxy leaving group. Only the more stable olefin isomer is produced since equilibration occurs in the enolate intermediate.

Another common α-silyl anion is produced by the halogen exchange from a methyl (but not other group) attached to silicon. Other α-silyl carbanions can be generated by other processes. Such anions lack the resonance stabilization of an ester group seen in the previous example. They are consequently less stable and must be generated under carefully controlled conditions. They are good nucleophiles and add effectively to aldehydes and ketones.

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