Cinchona Alkaloids as Stereoselective Organocatalysts for the Partial Kinetic Resolution Polymerization of rac-Lactide

This work investigates, for the first time, cinchona alkaloids such as cinchonidine (CD) and beta-isocupreidine (ICD) consisting of both a chiral nucleophilic amine catalyst site and an electrophilic hydroxy moiety, as bifunctional, stereoselective organocatalysts for the ring-opening polymerization (ROP) of L-lactide (L-LA) and rac-lactide (rac-LA). While the ROP of L-LA by CD is ineffective, the ROP of L-LA by ICD proceeds without noticeable epimerization, thus affording polylactide (PLA) with a quantitative isotacticity. The measured number-average molecular weight (M-n) is much higher than the expected Mn due to sluggish initiation by ICD, but when benzyl alcohol is added as an external protic initiator, the ROP is highly efficient and proceeds to high conversions without undesired transesterification reactions, thus producing PLA with a controlled Mn and a narrow molecular weight distribution of 1.12. More significantly, the ROP of rac-LA by ICD/alcohol affords crystalline isotactic-rich, stereogradient PLA that exhibits multiple melting-transition temperatures as a result of a partial kinetic resolution polymerization that preferentially polymerizes L-LA and kinetically resolves D-LA. Overall, this study uncovers the first kinetic resolution polymerization of rac-LA by an organocatalyst.