DIASTEREOSELECTIVITY IN THE PROTONATION OF ESTER ENOLATES - THE IMPORTANCE OF AGGREGATION WITH LDA

The effect of aggregation on the stereochemistry of electrophilic atta ck on ester enolate anions has been studied by comparing the diastereo selectivity of protonation of the LDA-generated dianion bf I 1 in THF/ DMPU with the H/D exchange of 3 under non-ion-pairing conditions. The LDA results are consistent with proton transfer to the:enolate occurri ng preferentially from the tightly complexed secondary amine. Proton s ources of varying steric requirements produced the same diastereomeric ratio, 63:37 2R,3R*/2R*,3S* of 2. Added BuLi and the omission of DMP U gave the same diastereomeric mixture. In contrast to the LDA results , ethyl beta-hydroxy- and beta-alkoxybutyrates undergo base-catalyzed H/D exchange largely through antiperiplanar transition states, with di astereoselectivity opposite of that found in-the LDA-enolate protonati on. Thus, the geometry of the LDA-enolate aggregate, rather than steri c and electronic factors in the monomer, is responsible for the stereo chemistry of enolate anion protonation. The lower diastereoselectivity in the H/D exchange of 6 in THF is accounted forby ion-pairing effect s, as the use of Me(4)NOD produced 92% of the 2R,3R* diastereomer; Us e of polar solvents in the H/D exchange also raised the diastereoselec tivity to a 10:1 ratio or higher.