Efficient and Chemoselective Synthesis of ω,ω-Heterodifunctional Polymers

We report a strategy for the preparation of semitelechelic polymers containing two distinct functionalities at one chain end by consecutive and chemoselective nucleophilic aromatic substitution reactions on 2,4,6-trichloro-1,3,5-triazine (TCT). Because of its commercial availability, well-defined nature, and ubiquity in biological applications, monomethyl ether poly(ethylene glycol) (mPEG) was chosen to demonstrate the utility of this ω,ω-heterodifunctional end-group modification strategy. TCT-functionalized mPEG underwent highly efficient ω,ω-heterodisubstitution via sequential chemoselective substitution with model thiols and amines. The efficiency of nucleophile conjugation to the polymer end group was confirmed by ¹H NMR spectroscopy and matrix assisted laser desorption-ionization time-of-flight mass spectrometry. In addition, density functional theory calculations provided insight into the importance of nucleophile addition order. This route introduces TCT derivatization as a powerful and facile tool to achieve specific polymeric end-group complexity and efficient heterogeneous functionalization.