Structure-selectivity relationship in alkyllithium-aldehyde condensations using 3-aminopyrrolidine lithium amides as chiral auxiliaries

A nonracemizing route to a set of chiral 3-aminopyrrolidines, based on 4-hydroxy-(L)-proline, is described. The induction potential of the lithium amides derived from these diamines has then been investigated in the asymmetric addition of alkyllithium compounds onto various aldehydes. Enantiomeric excesses up to 76% have been obtained in the case of the condensation of n-butyllithium onto o-tolualdehyde under standard experimental conditions (THF, -78 degrees C). Interestingly, the presence of a second asymmetric center, such as an alpha-methylbenzyl group, on the lateral 3-amino group gives access, according to its configuration, to one or the other of the 1-o-tolylpentan-1-ol enantiomers.