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

• DOI: 10.1016/j.tet.2012.07.006
• Publication Date: 2012-07-07T08:33:35Z
• Authors: Cecilia Andreu; Marcel·lí del Olmo; Gregorio Asensio
• Keywords: Aldol reaction; Aldol condensation; Enantiomeric excess; Chirality; Lewis acid catalysis

Abstract 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.