Abstract:The enantio-and diastereoselective epoxidation of a,b-unsaturated aldehydes in aqueous media was realized using a resin-supported peptide catalyst. Introducing the hydrophobic and bulky unnatural amino acid 3-(1-pyrenyl)alanine into the peptide sequence was effective for enhancing the reaction rate and enantioselectivity.Keywords: aqueous-phase catalysis; asymmetric catalysis; epoxidation; immobilization; peptides; proline In the last decade, peptides have been increasingly used as asymmetric catalysts for various organic reactions. Peptide catalysts provide products with high yield and selectivity under mild reaction conditions, and this is often realized by efficient substrate recognition through multiple interaction with the peptides having appropriate secondary structures.[1] Unlike conventional low-molecular-weight catalysts, peptide catalysts have a modular nature which enables modification through the change of the composition and the sequence of the amino acid monomers, including unnatural ones such as those shown in Figure 1.Recently, we have developed the resin-supported peptide catalyst 1 (Figure 2) which consists of the terminal five residues containing the b-turn motif d-ProAib [2] and hydrophobic a-helical polyleucine chain. The whole peptide is attached on the amphiphilic resin in order to avoid aggregation or sedimentation caused by its hydrophobicity. With use of catalyst 1, organocatalytic asymmetric Friedel-Crafts-type reactions, hydrogen transfer, and oxyamination have been realized under aqueous conditions in a highly enantioselective manner.[3] In some cases, employing an aqueous solvent instead of an organic solvent resulted in the acceleration of the reaction. Additionally, peptide-catalyzed reactions in aqueous media are of interest from the viewpoint of their relevance to enzymatic reactions which occur in water with extremely high efficiency and selectivity.Among a number of organocatalytic reactions, [4] the asymmetric epoxidation of enals using a chiral amine catalyst is important for the direct synthesis of optically active epoxides bearing formyl groups. [5,6] Some attempts have been made to extend this amine-catalyzed epoxidation to the reaction in aqueous media.[5b,e] However, the diastereoselectivity of the product was not so high compared with that of the reactions in organic solvent. We envisaged that a resinsupported peptide like catalyst 1 can perform the reaction in aqueous media both enantioselectively and