Effect of addition of Lewis/Brönsted acids in the asymmetric aldol condensation catalyzed by trifluoroacetate salts of proline-based dipeptides

Proline-based dipeptides catalyze aldol condensations with good yield and stereoselectivity after addition of zinc or sodium acetate to the trifluoroacetate peptide. The chirality of the N-terminal proline in the catalyst determines the absolute configuration of the aldol product, but stereoselectivity depends on the configuration of both amino acids, and is higher for the enantiomeric pair R-S, S-R. Regarding the nature of the second component, optimal results in both yield and stereoselectivity are obtained when neutral unbranched primary amino acids are used.