Kinetics preformed lithium enolate

The kinetically controlled nucleophilic addition of preformed lithium enolates onto carbonyl compounds is reversible with a low activation barrier, and the thermal conditions are likely to have a major impact on the stereoisomeric ratio of the final aldols through the retroaldolization and the thermodynamic equilibration of lithium enolates76. The tendency of aldolates to undergo retroaldolization increases with the stability of enolates, and when going from lithium to potassium. On the other hand, boron enolates usually undergo completely irreversible aldol reaction511,512. 

In aldol condensations involving preformed lithium enolates and aldehydes, complete kinetic stereoselection is observed (as illustrated in Scheme 39). When is bulky (e.g. t-butyl or trimethylsilyl) the (Z)-enolate gives the erythro-aldol and the ( )-enolate gives the threo-aldol. When R is smaller, the stereoselectivity diminishes or disappears. In contrast, a tetra-alkylammonium enolate reacts with benzaldehyde with equally high but opposite kinetic stereoselectivity. 

Using preformed lithium enolates, complete kinetic stereoselection has been achieved. The kinetic enolate of 2,2-dimethyl-3-pentanone is exclusively the Z isomer it adds to benzaldehyde to give only the erythro aldol product.Similar... 

Before commencing this discussion, it is appropriate to consider briefly the issue of kinetic versus thermodynamic control in the reactions of preformed Group I and Group II enolates and to summarize the structure-stereoselectivity generalizations that have emerged to date. It is now welt established that preformed lithium, sodium, potassium and magnesium enolates react with aldehydes in ethereal solvents at low temperatures (typically -78 °C) with a very low activation barrier. For example, reactions can often be quenched within seconds of the addition of an aldehyde to a solution of a lithium enolate. ... 

Stereoselective aldol condensation. Aldol condensation has been shown to be subject to kinetic stereoselection, with (Z)-enolates giving mainly the erythro-aldol and (E)-enolates giving mainly the (Areo-aldol. This observation has been extended to preformed (Z)- and (E)-lithium enolates generated under kinetic control with LDA in THF or ether at — 72°. When one of the alkyl groups is sterically demanding, complete kinetic stereospecificity can be obtained. As the bulk of the alkyl group decreases, stereoselection also decreases. Thus the kinetic enolate of ethyl /-butyl ketone (1) is the (Z)-isomer a, and it reacts with benzalde-hyde to form the erythro-aldol (2) with no detectable amounts of the threo-aldol. 

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