Binary Organocatalysts for Regioselective Ring‐Opening Polymerization of Methyl Glycolide †

Comprehensive Summary Poly(lactic‐ co ‐glycolic acid) (PLGA) has been widely employed for various biomedical applications owing to its biodegradability and biocompatibility. Particularly, the highly alternating PLGA exhibits a desirable degradation profile, making it an advanced platform for biomedical applications. In this contribution, we established a robust binary catalytic system of MTBD (7‐methyl‐1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene) and TU1 (1,3‐bis(3,5‐bis(trifluoromethyl)phenyl)thiourea), which facilitated highly regioselective ring‐opening polymerization (ROP) of methyl glycolide (MG) to deliver PLGA with regioselectivity up to 90% at room temperature. Remarkably, a 1 : 1 blend of alt ‐PLGA samples prepared from ( S )‐MG and ( R )‐MG formed a stereocomplex ( sc ‐PLGA) with T m of 178 °C. Preliminary in situ 1 H NMR study revealed the ring opening from the lactyl side. We believe a dual activation mechanism via hydrogen‐bonding interaction accounts for the improved regioselectivity.