Development of a Peptide‐Based Primary Aminocatalyst with a Helical Structure

A resin‐supported peptide with an N‐terminal primary amino group was developed as a primary aminocatalyst and used in the asymmetric Michael addition of nitromethane to α,β‐unsaturated ketones. These peptides with helical motifs, that is, polyleucine and a repeated Leu‐Leu‐Aib (Aib=2‐aminoisobutyric acid) sequence, efficiently catalyzed the reaction. The introduction of two tryptophan residues at the N‐terminus of the helical peptides improved the enantioselectivity of the reaction, and using the catalysts in aqueous media enhanced the reaction rate. The versatility of the optimum catalyst with the (Trp)2‐(Leu‐Leu‐Aib)3 sequence was demonstrated by applying it to other organocatalytic reactions such as the Michael addition of malonates to α,β‐unsaturated ketones and a three‐component, sequential reaction with methacrolein.