Covalently Preorganized (Thio)Urea–Alkoxide Organocatalysts Enable Controlled Synthesis of High‐Molecular‐Weight Polyglycolide

Polyglycolide (PGA) is a leading biodegradable polyester, but controlled access to high‐molecular‐weight PGA remains challenging. Here, we introduce a covalent preorganization strategy that merges H‐bond‐mediated monomer activation and alkoxide‐based chain propagation within a single molecular scaffold. Systematic variation of the H‐bond donor, substituent electronics, tether length, and counter cation identifies the thiourea‐based sodium alkoxide Cat. 7 as an optimal catalyst/initiator. Under mild conditions, Cat. 7 enables rapid and selective ring‐opening polymerization of glycolide, affording PGA with number‐average molecular weights up to 222.4 kDa (dispersity of 1.57, turnover number of 11 600, and turnover frequency of 483 h −1 ). Crystallographic, kinetic, spectroscopic, and computational studies support an intramolecular cooperative mechanism. The resulting high‐molecular‐weight PGA exhibits high crystallinity and tensile strength, highlighting (thio)urea‐alkoxide covalent integration as a powerful strategy for the precision synthesis of high‐performance biodegradable polyesters.