Synthesis of Well‐Defined PCL‐ b ‐PNVCL Block Copolymers via a Three‐Step Modular Route Combining ROP, RAFT/MADIX, and Click Chemistry

The design of amphiphilic block copolymers integrating biodegradable and thermoresponsive segments remains a significant challenge in polymer chemistry, particularly when precise architectural control is required. Among promising candidates, poly(ε‐caprolactone) (PCL) and poly( N ‐vinylcaprolactam) (PNVCL) stand out due to their respective biodegradability and stimuli‐responsive behavior. In this study, well‐defined poly(ε‐caprolactone)‐ b ‐poly( N ‐vinylcaprolactam) (PCL‐ b ‐PNVCL) block copolymers were synthesized via a modular three‐step strategy integrating ring‐opening polymerization (ROP), reversible addition–fragmentation chain‐transfer polymerization mediated by xanthates (RAFT/MADIX), and click chemistry. Alkyne‐terminated PCL (alkyne‐PCL) was obtained via ROP of ε‐caprolactone (ε‐CL) initiated by propargyl alcohol, while azide‐terminated PNVCL (PNVCL‐N 3 ) was synthesized by RAFT/MADIX polymerization of N ‐vinylcaprolactam (NVCL) using an azide‐functional xanthate RAFT agent. The two homopolymers were coupled via copper(I)‐catalyzed azide–alkyne cycloaddition (CuAAC) to yield PCL‐ b ‐PNVCL block copolymers. The CuAAC conditions were optimized by varying the catalytic systems (CuSO 4 ·5H 2 O/NaAsc and CuBr), reagent stoichiometries, and reaction temperature. Block copolymers formation and the presence of triazole linkages were confirmed by size exclusion chromatography (SEC), Fourier‐transform infrared (FTIR) spectroscopy, and proton nuclear magnetic resonance ( 1 H NMR) spectroscopy. Differential scanning calorimetry (DSC) measurements revealed amorphous or low‐crystalline characteristics in the resulting materials. This efficient and reproducible approach establishes a modular platform for designing biodegradable, biocompatible, and thermoresponsive block copolymers tailored for biomedical applications.