Stereoselective Alkylation of Glycine Units in Dipeptide Derivatives: “Chirality Transfer” via a Pivalaldehyde N,N-Acetal Center

Dipeptide esters (of glycylglycine, glycylalanine, alanylglycine) and aldehydes (isobutyraldehyde, pivalaldehyde, benzaldehyde) are condensed to (4-oxoimidazolidin-3-yl)acetates and -propionates (1–3). Lithium enolates of these derivatives are generated (deprotonation of the ring and/or side-chain α-carbonyl positions) with LDA, LDA/LiBr, or LHMDS and alkylated with high diastereoselectivity (products 4, 6, 7). Dipeptides of either R,R or S,S configuration can be prepared from the glycine-containing precursors. Surprising proton-transfer effects (Schemes VI-IX, XII) are interpreted as a consequence of “intimate complexation” among LDA, LiBr, lithium enolates, and diisopropylamine.