Wittig and related reactions

Review Comprehensive Organic Synthesis, Eds. B. M. Trost and I. Fleming, Pergamon, Oxford (1991), Vol 1, Part 3.1, p 729 

Quaternisation of triphenylphosphine with an alkyl halide gives a quaternary phosphonium halide (4) which under the influence of a strong base eliminates hydrogen halide to give an alkylidenephosphorane [(5), an ylide]. The latter reacts with an aldehyde or ketone to give first an intermediate betaine (6), which rearranges to the oxaphosphetane (7), which then under the reaction conditions eliminates triphenylphosphine oxide to form an alkene. 

The overall sequence is the Wittig reaction, and its great value lies in the fact that the mild conditions do not normally promote structural isomerisation for this reason alkenes of unambiguous structure may be synthesised. 

Since its discovery in 1953, the reaction has been extensively studied with respect to structural variation in the phosphonium ylide, in the range of functionalised aldehydes and ketones, in the nature of the bases and the polarity of the solvents that may be used, and in the mechanism of the reaction and the factors which influence the (E/Z) ratio. Many thousands of simple and complex syntheses have been effected and the method is widely exploited in research laboratories and in the industrial processes for syntheses in the steroid and carotenoid field. 

The preparative examples which are discussed below, and elsewhere in the text, have been selected to illustrate some of the considerations needed in the 

A retrosynthetic analysis for the alkene R1R2C=CH-R3 shows two possible carbonyl compounds as starting materials. 

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Wittig and related reactions in the synthesis of natural 0-heterocycles 97LA1283. 

This section deals with reactions that correspond to Pathway C, defined earlier (p. 64), that lead to formation of alkenes. The reactions discussed include those of phosphorus-stabilized nucleophiles (Wittig and related reactions), a a-silyl (Peterson reaction) and a-sulfonyl (Julia olefination) with aldehydes and ketones. These important rections can be used to convert a carbonyl group to an alkene by reaction with a carbon nucleophile. In each case, the addition step is followed by an elimination. 

The Wittig and Related Reactions of Phosphorus-Stabilized Carbon Nucleophiles... 

The Peterson olefination reaction involves the addition of an a-silyl substituted anion to an aldehyde or a ketone followed by the elimination of silylcarbinol either under acidic (awP -elimination) or basic (syn-elimination) conditions to furnish olefins178. Thus, Peterson olefination, just like Wittig and related reactions, is a method for regioselective conversion of a carbonyl compound to an olefin. Dienes and polyenes can be generated when the Peterson reaction is conducted using either an ,/l-unsaturated carbonyl compound or unsaturated silyl derivatives as reaction partners (Table 20)179. 

SECTION 2.4. THE WITTIG AND RELATED REACTIONS OF PHOSPHORUS-STABILIZED CARBON NUCLEOPHILES... 

Abell, A. D. Edmonds, M. K. The Wittig and Related Reactions. In Organophosphorus Reagents Murphy, P. J., Ed. Oxford University Press Oxford, 2004 pp 99-127. 

Table 11. Selected Wittig and Related Reactions of Cyclobutanones3...

By Wittig and related reactions (3-Dimethylaminopropyl)-triphenylphosphorane, 119 Sodium amide, 278 Vinyl(triphenyl)phosphonium bromide, 343 (E)-Alkenes By elimination reactions Arylselenocarboxamides, 22 Dichlorobis(cyclopentadienyl)-titanium, 102 Hydrogen peroxide, 145 From three-membered heterocycles Tributyltinlithium-Trimethylalu-minum, 320 Trisubstituted alkenes Chloromethyldiphenylsilane, 74 Organocopper reagents, 207 Alkenes (Methods to form alkenes)... 

The Wittig and related reactions have been reviewed in the context of natural product synthesis 120 mechanistic studies of the Wittig reaction have also been reviewed with particular reference to asymmetric induction.121... 

Tervalent phosphorus has a high affinity for oxygen and the P=0 bond once formed is very strong. This fact, which also provides the driving force for the Wittig and related reactions, has led to the widespread use of P(III) compounds for direct deoxygenation of epoxides, ozonides, carbonyl compounds, and both N- and 5-oxides.2... 

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