Pentafluorophenyl-Tagged Poly(2-isopropenyl-2-oxazoline) as a Highly Reactive Precursor for <i>para</i> -Fluoro-Thiol Click Chemistry

Poly(2-isopropenyl-2-oxazoline) (PIPOx) is a versatile postpolymerization modification platform, yet its reactions have so far been limited to direct additions of thiols and carboxylic acids with variable efficiency. Here, we show that the reaction of PIPOx with 2,3,4,5,6-pentafluorothiophenol (PFTP) rapidly and cleanly generates poly(N-(2-((perfluorophenyl)thio)ethyl)methacrylamide) (PPFPTEMA), a highly reactive precursor for para-fluoro-thiol (PFT) click chemistry, featuring fast kinetics, equimolarity, orthogonality, and facile product isolation. A wide array of commercially available thiols react quantitatively and selectively with PPFPTEMA, enabling the synthesis of well-defined polymethacrylamides with diverse side-chain functionalities, including ionizable groups, supramolecular motifs, natural compounds, drugs, fluorescent tags, and polymers. The high efficiency and orthogonality of the PFT click reaction also allow multiple thiols to be combined to precisely tailor the copolymer composition. Importantly, when using thiol excess, the pentafluorophenyl groups in PPFPTEMA are found to undergo multiple substitutions under mild conditions, offering an unprecedented level of synthetic flexibility for designing functional polymers. Overall, this work seamlessly integrates PFT click chemistry into the PIPOx platform, establishing a powerful modular framework for the precision synthesis of multifunctional polymers.