Synthesis of Click-Ready Aminooxy-Terminated Poly(ε-caprolactone) Oligomers for Oxime Ligation

Oxime ligation, a chemoselective coupling between carbonyl compounds and aminooxy groups, enables conjugation under mild and aqueous conditions. Here, we integrate this reaction with degradable polymers through a one-pot synthesis of aminooxy-functionalized poly(ε-caprolactone) (PCL) oligomers. The bifunctional initiator 6-(tert-butyloxycarbonylaminooxy)-1-hexanol was employed for simultaneous ε-caprolactone ring-opening polymerization and in situ Boc-deprotection catalyzed by methanesulfonic acid (MSA). Optimized conditions afforded >95% conversion for both reactions, while maintaining well-defined oligomer structures (DP = 5-20). The resulting NH₃⁺-O-PCL oligomers underwent rapid and efficient oxime ligation with a diverse set of aldehydes and ketones, achieving >90% conversion within 1-2 h at room temperature. Reactions proceeded effectively even in mixed aqueous solvents (H₂O/MeOH/CHCl₃ = 1:3:1), for example, with the reducing ends of glucose and xylose. This work establishes a straightforward, water-tolerant synthetic platform for preparing "click-ready" degradable polymers, enabling broad integration with biobased and functional substrates.