Bifunctional Fluoroalcohol Catalysts Enabled Sustainable Synthesis of Poly(amino acid)s †

Main observation and conclusion A series of novel bifunctional single‐molecule hydrogen‐bonding organocatalysts based on fluorinated tertiary alcohol were synthesized to mediate the metal‐free polymerization of α ‐amino acid N ‐carboxyanhydride (NCA) monomer. Through the screening of catalysts, the polymerization catalyzed by the preferred bifunctional fluoroalcohol catalyst proceeded in a fast and controlled manner, affording high molecular weight polypeptide up to 35.2 × 10 4 Da with relatively narrow molecular weight distribution ( Đ < 1.20). A phenomenon of self‐accelerating effect of polymerization induced by α ‐helical structure of polypeptides was observed, and a possible polymerization pathway has been discussed.