Michael reactions of pseudoephedrine amide enolates: effect of LiCl on syn/anti selectivity.

The stereochemical outcome of the asymmetric Michael reaction of pseudoephedrine amide enolates changes dramatically in the presence of LiCl. Reaction of the enolate in the absence of LiCl results in formation of the anti Michael adduct with high selectivity, whereas in the presence of lithium chloride the syn adduct is favored. This method provides access to enantiomerically enriched trans-3,4-disubstituted delta-lactones from the anti Michael adducts by a two step reduction/lactonization sequence. Information obtained from NMR studies indicates that, under both enolization conditions, the (Z)-enolate is formed. A model to explain the turnover in selectivity based on NMR evidence is presented.