Stereoselective ring opening polymerization of lactide using chiral aluminum salan catalysts

The stereocontrolled ring-opening polymerization of lactide via rational catalyst design remains a challenge due, in no small part, to the presence of the various stereoisomers of lactide and the resulting structural complexity that arises along the reaction profile. In practice, stereochemistry leads to polylactides with different structures and properties, although the syndiotactic product is desired. Density functional theory (DFT) can contribute by identifying the underlying non-covalent interactions that favor one reaction profile over another. Herein, we investigate the initiation step of a chloride-substituted, bipyrrolidine-based aluminum-alkoxy salan catalyst that has shown a kinetic preference for the stereoselective ring-opening of meso-lactide at the carbonyl unit adjacent to the R stereocenter. Moreover, when experiments are performed under thermodynamic control, the initiation product in which the S stereocenter is ultimately adjacent to aluminum is favored. An exhaustive conformational search of both minima and transition state structures reveals that DFT reaction mechanisms are consistent with these observations. Specifically, the rate-determining transition states corresponding to ring opening at the R stereocenter are stabilized by crucial ligand-chain non-covalent interactions including hydrogen bonding. Consequently, the rate determining transition state for ring-opening at the S-stereocenter lies only 0.6 kcal mol^-1 higher in energy, further emphasizing the importance of using conformational sampling in modeling such processes.