Regioselective Ring-Opening Polymerization of Asymmetric Cyclic Dimers for Polyester-Based Alternating Copolymers.

Sequence-controlled polyester-based alternating copolymers have attracted significant interest due to their biocompatibility, biodegradability, closed-loop recyclability, and hydrolytic degradability, offering broad potential in biomedical and sustainable materials. Among the available strategies, regioselective ring-opening polymerization (ROP) of asymmetric cyclic di(thio)esters and cyclic(ester-amide)s has emerged as a promising approach for constructing alternating copolymers with precise sequence- and stereo-control, structural diversity, and tunable properties. This review classifies asymmetric cyclic monomers into two categories: (1) monomers with two aliphatic ester bonds, where regioselectivity is mainly dictated by steric differences and typically requires tailored metal catalysts; and (2) monomers with chemically distinct reactive sites (e.g., phenolic ester, thioester, or amide vs. aliphatic ester), which enable near-perfect regioselectivity using simple catalysts. Recent progress in the synthesis of alternating aliphatic copolyesters, poly(phenolic-alt-aliphatic ester)s, poly(ester-alt-thioester)s, and poly(ester-alt-amide)s is highlighted, emphasizing their enhanced degradability, recyclability, and mechanical performance. Key advances in catalyst optimization, mechanistic understanding, quantification of regioselectivity, and the structure-property relationships of alternating copolymers are summarized. Finally, future directions are discussed, including rational catalyst design, expansion to new monomer architectures, and the systematic evaluation of how regioselectivity governs alternating copolymer properties.