Betaine rationale

In light of this statement, and of contrary experimental evidence that had already begun to appear by 1970 (1), it may be difficult to understand why the betaine rationale became so widely accepted (2a-e, h). Readers who are interested in the controversies and the complicated chronology of the mechanistic investigations between 1970 and 1990 may want to consult... 

Nevertheless, evidence had begun to accumulate that could not be easily reconciled with the assumptions inherent in the betaine rationale as summarized in Figure 1. Riichardt et al. (1S) had found a suprising similarity in the reaction rates for PhjP=CHC02Et with various aldehydes in benzene and in acetonitrile. If the mechanism involved rate-determining betaine formation. 

Spiroacylal 2 was designed under the rationale that the constraint of the carbonyl groups into a conformation in which overlap of their 7r-orbitals with the bent bonds of the cyclopropane is assured should dramatically increase the vulnerability of the cyclopropane toward nucleophilic attack.8 Experimental support for this notion is abundant.8 Spiroacylal 2 is considerably more reactive than 1,1-dicarbethoxycyclopropane in such reactions. For instance, reaction of 2 with piperidine occurs at room temperature. The corresponding reaction in the case of the diester is conducted at 110°C.5 Reactions with enolates also occur under mild conditions.8 Compound 2 reacts with the weak nucleophile pyridine at room temperature to give a betaine.8 An illustrative mechanism for the reaction of the acylal 2 with aniline to afford 2-oxo-l-phenyl-3-pyrrolidinecarboxylic acid (3) is... 

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. 

---