Synthesis of Optically Active β-Peptides by Stereospecific Step-Growth Anionic Polymerization of Various Acrylamide Derivatives

β-Peptides have attracted increasing attention because of their high stability and ability to form unique secondary structures. However, they are generally prepared from chiral β-amino acids or chiral β-lactams, which are limited in availability and often difficult to synthesize. Therefore, synthesis from easily accessible compounds is desirable. From the viewpoint of their structures, β-peptides can be regarded as structural isomers of polyacrylamides. Hydrogen-transfer polymerization of acrylamide derivatives has been reported using base catalysts, in which step-growth polymerization proceeds via intermolecular anionic addition of amide groups to vinyl groups, giving polymers with β-peptide backbones. However, the synthesis of optically active β-peptide derivatives through this approach has rarely been reported. In this study, we investigated the synthesis of optically active β-peptide derivatives via stereospecific step-growth anionic polymerization of acrylamide derivatives using chiral countercations generated from base catalysts and chiral ligands. First, step-growth anionic polymerization of crotonamide, which bears a methyl group at the β-position of acrylamide, was examined using potassium tert-butoxide (KOtBu) in combination with various nitrogen-based chiral multidentate ligands, such as bisoxazoline (Box) ligands. Regardless of the presence or absence of the ligands, polymerization proceeded, affording polymers with high molecular weights (M_n ≥ 10³). In contrast, the specific optical rotation values of the obtained polymers significantly varied depending on the ligands employed. In particular, the combination of KOtBu and an indane-type Box ligand bearing dimethyl groups at the central carbon gave an optically active polymer with a specific optical rotation of +22. Additionally, the effects of monomer substituents and chiral base catalysts on the stereoselectivity and optical activity were also investigated.