From carbonyl to sulfonyl: Unlocking advanced polymers with SuFEx-enabled “macroisosteres”

To help guide future synthetic efforts toward advanced polymers with enhanced performance across uncharted chemical space, this review introduces the concept of “macroisostere” design, in which functional groups in high-commodity polymers are replaced with structurally analogous motifs. As a case study, we focus on the nascent family of sulfonyl (–SO 2 –)-containing polymers as “macroisosteres” of traditional carbonyl (–CO–)-based macromolecules. Historically, this class of polymers has remained largely underexplored due to limited synthetic accessibility compared to their carbonyl counterparts. The advent of Sulfur(VI) Fluoride Exchange (SuFEx) click chemistry has changed this landscape, enabling the efficient synthesis and systematic study of sulfonyl polymers and their physicochemical properties. In this review, we contrast classical synthetic routes with SuFEx-based strategies, showcasing how this powerful click chemistry provides access to materials with tunable properties including thermal, mechanical, and optoelectronic behaviors alongside sustainability. We also highlight the unique opportunities SuFEx offers for precision polymer synthesis, including the construction of macromolecules with chiral backbones arising from stereogenic S(VI) centers and the development of sequence-controlled architectures and post-polymerization modifications enabled by the orthogonality of SuFEx relative to other click reactions.