An Orthogonal Modular Approach to Macromonomers Using Clickable Cyclobutenyl Derivatives and RAFT Polymerization

A series of cyclobutene-based macromonomers derived from monomethyl ether poly­(ethylene oxide) (PEO), poly­(ethyl acrylate) (PEA), poly­(<i>N</i>-isopropylacrylamide) (PNIPAM), and PEO-<i>b</i>-PNIPAM were synthesized by “click” copper-catalyzed azide–alkyne cycloaddition (CuAAC) and reversible addition–fragmentation chain transfer (RAFT) polymerization. First, original di- and trifunctional cyclobutene precursors with azido, alkyne and/or chain transfer agent were successfully obtained and fully characterized. Azido- and alkyne-functionalized cyclobutenes were then conjugated with modified PEO bearing azido or alkyne groups, resulting in cyclobutene-based PEOs in quantitative conversions as ascertained by NMR spectroscopy and MALDI–TOF mass spectrometry. The new chain transfer agent-terminated cyclobutene was used to mediate the RAFT polymerization of ethyl acrylate and <i>N</i>-isopropylacrylamide. Well-defined polymers with controlled molecular weights (<i>M</i>_n = 3700–11 500 g·mol^–1) and narrow molecular weight distributions (PDI = 1.06–1.14) were thus obtained that retain the cyclobutene functionality, demonstrating the orthogonality of the RAFT process toward the cyclobutenyl insaturation. Combination of CuACC and RAFT polymerization was used to afford PEO-<i>b</i>-PNIPAM block copolymer functionalized by a cyclobutene end-group