Organocatalyzed ring-opening polymerization of meso-lactide reveals competing mechanisms of stereocontrol

The mechanism for the ring-opening polymerization (ROP) of meso-lactide (LA) promoted by the chiral thiourea-amine organocatalyst has been elucidated through density functional theory (DFT) calculations. A comprehensive description of the process was obtained by accounting for the distinct reactivity of the two ring-opening sites of meso-LA with the carbonyl group adjacent to the (R) or (S) stereogenic atoms and the two monomer enantiofaces (re vs si). This mechanistic complexity gives rise to multiple competing pathways with comparable activation barriers, in line with the experimental Pm value of 0.62, which indicates the formation of a weakly syndiotactic polylactic acid (PLA). Compared to the ROP of rac-LA (Pm = 0.90), the reduced selectivity is attributed to a weaker and less cooperative (antagonistic) interplay between enantiomorphic site (ESM) and chain-end (CEM) control models, leading to diminished energetic discrimination among the competing pathways.