Stride Strategy to Enable a Quasi-ergodic Search of Reaction Pathways Demonstrated by Ring-opening Polymerization of Cyclic Esters

Coordination-insertion ring-opening polymerization (ROP) of cyclic esters is an industrial way to synthesize polyesters, which are widely applied in biomedical and environment-benign fields. However, the rate-determining transition state (TS) identified by the conventional reaction pathways (pathway A and pathway B) presented in the literature did not well describe the structure-reactivity relationship. The misidentification of the rate-determining TS might arise from the less ergodicity in the search of reaction pathways. Herein, we suggested a stride strategy based on the insight that even a partial double bond is rotatable at the catalysis temperature. As a result, we revealed a new reaction pathway, pathway C with a torsion transition state TSC2, by density functional theory (DFT). We also carried out kinetic experiments of ROP of D-lactide (D-LA), L-lactide (L-LA), ε -caprolactone (CL), and δ -valerolactone (VL), using poly(ethylene glycol) as the initiator and stannous octoate as the catalyst. The excellent linearity between the calculated free energy barriers and logarithms of the experimental kinetic constants of the two kinds of lactide and lactone monomers, was established, validating the quasi-ergodic search of reaction pathways and the scaling predicted by transition state theory. The linearity was highly predictive for the other lactide and lactone monomers, demonstrated by glycolide (GA) and trimethylene urethane (TU).