Lithium halide betaine adducts

Betaine precipitates have been isolated in certain Wittig reactions, but these are betaine-lithium halide adducts, and might just as well have been formed from the oxaphosphetane as from a true betaine. However, there is one report of an observed betaine lithium salt during the course of a Wittig reaction. In contrast, there is much evidence for the presence of the oxaphosphetane intermediates, at least... 

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... 

Methods A, D, and E suffer from the inherent limitation that they deliberately generate a betaine as the precursor of the oxaphosphetane. Since there is no assurance that the reaction of an ylide with an aldehyde would involve the same ionic intermediate (19,21) these control experiments may provide opportunities for stereochemical equilibration that may not be available to the corresponding Wittig reactions. If the oxaphosphetane generated by methods A or E is stable enough to observe directly, then it is usually possible to distinguish between oxaphosphetane equilibration, betaine equilibration, and other mechanisms for loss of stereochemistry (21 c). However, this is not possible for oxaphosphetanes that contain unsaturated substituents at Cj because oxaphosphetane decomposition is fast at — 78°C (21c). In these examples, method A (like method D or E) can only establish an upper limit for equilibration of all of the conceivable intermediates betaines, betaine lithium halide adducts, oxaphosphetanes, and so on. 

Lithium Halide-catalyzed Reversal via Betaine Lithium Halide Adducts. This is the most common mechanism for loss of stereospecificity under Wittig conditions and often contributes to the stereochemical outcome of bezaldehyde reactions in the presence of lithium ion. The process is most facile for ylides containing anionic (alkoxide, carboxylate, or amido) substituents. 

It is likely that the ( )-alkene selective reactions of anionic ylides are due to equlibration of the betaine lithium halide adduct as discussed earlier. However, the balance is delicate and small structural changes can have surprising consequences. Thus, Corey s stereospecific trisubstituted alkene synthesis via /3-oxido ylides (Table 10) is clearly under dominant kinetic control, even though lithium ion is present and aromatic aldehydes can be used as the substrates (54,55). The only obvious difference between the intermediates of Table 10 and oxido ylide examples such as entry 11 in Table 21 is that the latter must decompose via a disubstituted oxaphosphetane while the stereospecific reactions in Table 10 involve trisubstituted analogues. Apparently, the higher degree of oxaphosphetane substitution favors decomposition relative to equilibration. There are few easy and safe generalizations in this field. Each system must be evaluated in detail before rationales can be recommended. 

Some of the most profound lithium ion effects are observed in diethyl ether, benzene, or toluene, and the literature on Wittig reactions under these conditions contains a number of results that appear to be somewhat contradictory. The reason for this lack of consistency may be related to issues of lithium halide or betaine adduct solubility. Thus, Bergelson and Shemyakin et al. (5c, d) were able to show that ylide solutions prepared in benzene behaved differently if they were filtered to remove precipitated salts prior to use (compare Table 11, entries 3 and 4 entries 47 and 48). Later, it was shown that filtered toluene solutions of Ph3P=CHCH3 obtained from the phos-phonium bromide using butyllithium contain <0.1% bromide according to elemental analysis (18b). Therefore, the dramatic change in the alkene ratio... 

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