Of Wittig reaction

There have been many applications of the Wittig reaction in multistep syntheses. The reaction can be used to prepare extended conjugated systems, such as crocetin dimethyl ester, which has seven conjugated double bonds. In this case, two cycles of Wittig reactions using stabilized ylides provided the seven double bonds. Note the use of a conjugated stabilized ylide in the second step.250... 

The alkyl halide must be one that is reactive toward SN2 displacement. Alkyltriphenylphosphonium halides are only weakly acidic, and strong bases must be used for deprotonation. These include organolithium reagents, the sodium salt of dimethyl sulfoxide, amide ion, or substituted amide anions such as hexamethyldisilylamide (HMDS). The ylides are not normally isolated so the reaction is carried out either with the carbonyl compound present or it may be added immediately after ylide formation. Ylides with nonpolar substituents, for example, H, alkyl, or aryl, are quite reactive toward both ketones and aldehydes. Scheme 2.16 gives some examples of Wittig reactions. 

You notice that we have drawn the intermediate ylid as an enolate just to emphasize that it is an enolate derivative it can also be represented either as the ylid or as a C=P phosphorane structure. If we look at the details of this sort of Wittig reaction, we shall see that ylid formation is like enolate anion formation (indeed it is enolate anion formation). Only a weak base is needed as the enolate is stabilized by the Ph3P+ group as well. 

The remainder of this chapter will detail examples of the main types of Wittig reaction using examples to highlight (i) those factors that influence the stereoselectivity of the above methods, (ii) modifications to the standard procedures, and (iii) uses of these reactions in organic synthesis. 

Schlosser modification of Wittig reaction The presence of soluble metal salts such as lithium salts decreases the aVfrans-selectivity. The normal Wittig reaction of non-stabilized ylides with aldehydes gives Z-alkenes. The Schlosser modification of the Wittig reaction of non-stabilized ylides furnishes -alkenes. In the presence of lithium halides oxaphosphetanes can often be observed, but betaine-lithium halide adducts are also formed. If lithium salts are added to the equilibrium, oxaphosphetane formation and elimination of... 

Z)-condenses with aldehydes in a (Z)-stereoselective Wittig reaction to afford diethyl acetals of (Z)-a,jS-unsaturated aldehydes in 57-86% yield. Hydrolysis of the acetals with p-TsOH as catalyst in acetone-water or with moist silica gel (2 days at 23°) affords the corresponding (Z)-unsaturated aldehydes in 47-98% yield. The product usually contains 4-14% of the (E)-isomer. These results contrast with those of Wittig reactions of formylmethylenetriphenylphosphorane and l,3-dioxolan-2-ylmethylenetriphenyl-phosphorane (5, 269), which afford (E)-unsaturated aldehydes. 

FIGURE 7.14 Example of Wittig reactions with sugars. 

SCHEME 7.42 Mechanism of Wittig reactions with lactols. 

There. ire many ways o make the other isomers (Z,Z- t.t- Z,T dienes and you might have used alternative styles of Wittig reactions or reduction of alkyjies (pp. 813-19) or other methods described in Chapter 31. 

McEwen, W. E., Beaver, B. D., Cooney, J. V. Mechanisms of Wittig reactions a new possibility for salt-free reactions. Phosphorus and... 

McKenna, E. G., Walker, B. J. The mechanism and stereochemistry of Wittig reactions of phosphonium ylide-anions. Phosphorus, Sulfur Silicon Relat. Elem. 1990, 49-50, 445-448. 

Harding, K.E., and Tseng, C.-Y, Observations on the steric requirement of Wittig reactions with triaUcylphosphonoacetates, J. Org. Chem., 40, 929, 1975. 

Another synthesis of isoochracinic acid (27), utilises an interesting application of Wittig reaction. 3-Methoxyphthalic anhydride on reaction with carbobenzyl-oxymethylenetriphenyl phosphorane, followed by hydrogenation and demethylation furnishes 21. It may be noted that 3-methoxyphthallc anhydride can be readily obtained by aromatic lithiation of N,N-diethyl w-methoxy benzamide followed by treatment with COj (vide supra). 

Figure 2.8.1 Example of Wittig Reactions with Sugars ...

Examples of standard uses of Wittig reactions to prepare prostaglandin analogues include a synthesis of PGF2a- ... 

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