Wittig reaction substituent effects

The reactivity of ylides is influenced not only by the substituents R and R, but also by the character of the so-called stationary substituents on the phosphorus atom. If the phenyl groups normally used are replaced by electron donors such as alkyl groups, the electron density on the phosphorus and thus the nucleophilicity of the ylide are increased. The structure of the stationary substituents on the phosphorus has a considerable influence on the stereochemistry of Wittig reactions. These effects are discussed in Section C.2. 

The stereoselectivity of the Wittig reaction is believed to be the result of steric effects that develop as the ylide and carbonyl compound approach one another. The three phenyl substituents on phosphorus impose large steric demands that govern the formation of the diastereomeric adducts.240 Reactions of unstabilized phosphoranes are believed to proceed through an early TS, and steric factors usually make these reactions selective for the d.v-alkcnc.241 Ultimately, however, the precise stereoselectivity is dependent on a number of variables, including reactant structure, the base used for ylide formation, the presence of other ions, solvent, and temperature.242... 

The carbonyl- 14C KIEs in the title reaction system (equation 225), which gives a nearly 50 50 mixture of cis-trans isomers, depends very much on the ylide used430, and indicate that the reactions proceed via cycloaddition TS of considerable nucleophilic character, inferred also from the substituent effects studied. Positive p values indicate that the Wittig reaction is nucleophilic in nature. Assuming as before the four-centered TS, the authors430 conclude that the C—C bond formation is much advanced of the P—O bond formation in the TS and that the carbonyl-carbon KIE are expected to be larger for later TS salt-free reaction410 (more reactant-like for Li salt present in reaction). 

Triphenylarsine oxide reacts with a number of electrophilic acetylenes having electron-withdrawing substituents in what are, in effect, reverse-Wittig reactions, thereby providing stable arsonium ylides (equation 31) Reaction is presumably initiated by Michael-type reaction of the oxide with the alkyne, as exemplified in equation 32. As would be expected from such a mechanism, use of an unsymmetric alkyne, as in the foregoing example, results in virtually regiospecific attack by the oxide to give the product shown. 

These marked metal ion effects (7), in conjunction with well known solvent and substituent effects, suggest that an ionic mechanism is operative in the metal ion catalyzed Wittig reaction (7Z>). An ionic mechanism for the Wittig half-reaction of benzylidenetriphenylphosphorane with aldehydes can be envisioned as shown in Figure 1. 

Consequently, phospha-l,2-dioxetanes are the only reasonable intermediates that produce the excited carbonyl fragments and simultaneously satisfy the experimental results in the present study. In this study, the substituent effect on the ring closure step in the oxy-Wittig type reaction was revealed by chemiluminescence decay. The promotion of the ring formation results in the... 

A further mechanistic study of the Wittig reaction between lithium-free isopropylidenetriphenylphosphorane (58) and benzophenone (59) in THF was shown by 51p n.m.r. to proceed via the oxaphosphetan intermediate (60) with ki= 1.3 x 10"3 lmol l s l, k2 = 4.0 x lO" s l and k3 = 7.0 x 10"4 s l. In addition carbonyl kinetic isotope effects and a value of p = +1.4 based on variations of substituents in the aryl group of the ketone, were consistent with rate-determining formation of the oxaphosphetan (60).23... 

It is too early to decide whether semiempirical computations can successfully evaluate TS models such as 117-124 given the current level of precision. This situation is likely to change as the theoretical methods refine their phosphorus parameters and their ability to mimic solvation effects. Table 22 provides many opportunities to test computational TS predictions. Selectivity in the Wittig reaction depends on substituents, not on some fundamental property of phosphorus ylides. Thus, any successful theoretical analysis of the selectivity issue will need to explain the substituent-induced differences in kinetic Z E ratios. 

Hwang et al. [24] studied the Wittig reaction of benzyltriphenylphosphonium (BTPP) salts and benzaldehydes via ylide-mediated PTC. They concluded that the reaction of benzylidenetriphenyl phosphorane and the benzaldehyde in the organic phase is the decisive step for stereoselectivity. The order of effectiveness of substituents is CF3 > (Cl, Br) > MeO > F > NO2. Satrio and Doraiswamy [25] proposed a case study for the production of benzaldehyde in a possible industrial application of PTC. The reaction between benzyl chloride and hypochlorite anion is... 

The stereoselectivity of the Wittig reaction depends, not only on the substituents, but also on the conditions under which the reaction is effected. The presence of lithivun salts tends to favour the fJ-alkene, so reactions in which the Z-alkene is desired are often carried out using sodium or potassium bases. It is possible to obtain high yields of the fJ-alkene from a non-stabilized phosphonium ylide by deprotonation, then reprotonation of the intermediate oxaphosphetane or betaine. An especially useful application of the Wittig reaction is in the formation of exo-cyclic double bonds. Thus, cyclohexanone and (methylene)triphenylphosphorane give (methylene)cyclohexane, whereas the use of the Grignard reaction followed by dehydration leads to the endocyclic isomer. 

Ketals are converted to allyl vinyl ethers after Wittig olefination [14]. Wittig reactions permit the incorporation of various substituents into the allyhc terminal of the ether. Enol ethers have been conveniently prepared by cleavage of acetals with various Lewis acids. Cleavage of the ketals with the Lewis acid, for example, triethylsilyl triflate, in the presence of diisopropylethylamine in refluxing 1,2-di-chloroethane afforded the enol ethers (Eq. 3.1.9). The resulting enol ethers were then heated to effect the Claisen rearrangement without isolation. 

The often superior properties of diphenylphosphine oxides, compared with the corresponding phosphonates and phosphonium salts, has led to the development of AT-morpholinomethyldiphenylphosphine oxide (42), a new formyl anion equivalent. This new reagent converts aromatic and aliphatic aldehydes into their homologous enamines by a Horner-Wittig reaction (Scheme 44). To effect this reaction satisfactorily with ketones a less strongly basic amino substituent is necessary (e.g. AT-methylaniline). 

A computational study has examined the effects of substituents on the sulfur-Wittig reaction of H2S=CH2 with a range of formyl (0=CH-R) substrates R = H, F, Cl, Me, OMe, NMe2 and... 

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