Degradable Telechelic Polythioesters from Activated Diesters and Their Site-Selective End-Group Functionalization

In light of growing interest in developing strategies for new classes of degradable polymers, polythioesters (PTEs) remain relatively underexplored and are predominantly prepared via the ring-opening polymerization (ROP) of cyclic monomers. We report here a versatile, controllable step-growth methodology for the synthesis of telechelic PTEs directly from simple dithiols, exploring activated-ester-mediated thioesterification chemistry. Polycondensation reaction between a pentafluorophenyl (PFP)-based diester of adipic acid with two structurally different dithiols, viz., linear 1,6-hexanedithiol and the polar 3,6-dioxa-1,8-octanedithiol, afforded well-defined telechelic polythioesters with near-quantified monomer conversion under mild conditions (∼75 °C) using 4-dimethylaminopyridine (DMAP) as an organocatalyst in DMF as the solvent. The highly reactive nature of the PFP-ester facilitated efficient polymerization without the need to remove the released byproduct (pentafluorophenol), which is otherwise essential in traditional polycondensation reactions to prevent backward reactions and drive the equilibrium forward toward high-yield polymers. Detailed kinetic analysis demonstrated the efficacy of this methodology, which was accelerated by DMAP acting as a nucleophilic catalyst. Moreover, this strategy enables tuning of the degree of polymerization by varying the stoichiometric ratio between the activated diester and the dithiol. A stoichiometric excess of either the dithiol or the diester enabled the synthesis of thiol-terminated or PFP-ester-terminated telechelic PTEs, which were subjected to site-selective postpolymerization end-group modification via a thiol–ene click reaction or transesterification, respectively. The versatility of the approach was further demonstrated through a one-pot synthesis of a pyrene end-capped PTE using pyrene methanol as a “monofunctional impurity” during the polymerization reaction between the diester and the dithiol. Thermogravimetric analysis revealed that the resultant PTEs are highly stable but can be degraded by aminolysis under mild phosphate-buffered conditions. Comparing the thermal properties of a PTE with those of a structurally analogous polyester of comparable molecular weight indicated higher crystallization and melting temperatures for the polythioester analogue. Overall, this step-growth approach offers a straightforward route to PTEs by bypassing the need to synthesize sulfur-containing cyclic monomers essential for ROP, thereby offering the clear advantages of synthetic simplicity, structural tunability, and end-group functionalization.