Azaenol ates

The diastereoselectivity observed during the addition of (61c) to isobutyraldehyde stands in marked contrast to the significantly lower selectivity (1.5 1) that was previously observed when the chiral 2-methyloxazoline (59) was used as the nucleophilic partner (vide supra). The enhanced diastereoselection in the reaction involving (61c) is presumably a consequence of internal lithium chelation, which enhances both the selectivity in the deprotonation step as well as the diastereofacial selectivity in the nucleophilic addition to the aldehyde. For example, in separate experiments it was determined that metallation of (61c) proceeded with a (Z) ( ) diastereoselectivity of >9 1. Subsequent reaction of this (Z)-azaenol-ate with isobutyraldehyde via the chelated, chair-like transition state depicted in (64 R = Me), in which steric interactions between the reacting residues are minimized, would lead preferentially to the anti isomer (62c). For the additions involving (59), examination of the related transition state (64 R = H) clearly reveals that the facial selectivity should be somewhat less. 

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