Precision Synthesis of Polyacetal/Polyester Block Copolymers from a Four-Component Mixture Involving Epoxide Congeners via Switchable Polymerization

Abstract Sequence-controlled polymers have attracted interest due to their structural precision, which enables for functions reminiscent of natural macromolecules. Switchable polymerization offers a powerful platform for one-pot block copolymer synthesis, but maintaining orthogonal chemoselectivity becomes challenging when monomer mixtures involve congeners with similar reactivities. Even when such selectivity is established, additional comonomers can generate active species that perturb the original chemoselectivity. Here, we report a switchable polymerization strategy that enables the precise one-pot synthesis of polyacetal-block-polyester copolymers from a four-component mixture of epoxides, o-phthalaldehyde (OPA), and nadic anhydride (NA). Using an organoboron catalyst, the system exhibits strict chemoselectivity: at room temperature, only the terminal epoxide (PO) and OPA copolymerize to form the polyacetal block, while the internal epoxide (CHO) and NA remain inert; upon heating, the system switches to CHO/NA copolymerization to construct the polyester block. Comprehensive characterization confirmed that the bulky anhydrides NA, OA, and MeNA yielded tapering-free block architectures, while the less sterically hindered anhydrides gave only minor tapering, and mechanistic studies reveal that the orthogonal selectivity arises from distinct kinetic preferences of the resting state at each stage. The method accommodates various epoxides and anhydrides, providing a versatile platform for precision synthesis of sequence-controlled block copolymers.