Flow-IEG Enables Programmable Thermodynamic Properties in Sequence-Defined Unimolecular Macromolecules

Polymer Chemistry 8, 5786-5794, DOI: 10.1039/C7PY01204G

Monodisperse oligomers are important intermediates for studying structure–property relationships in soft materials but are traditionally laborious to synthesize. A semi-automated synthetic system that combines the benefits of telescoped reactions in continuous flow with iterative exponential growth (IEG) greatly expedites this process and makes the rapid synthesis of structurally diverse oligomer libraries practical. Herein, the coupling chemistry in the Flow-IEG system has been upgraded and expanded to include both 1,4- and 1,5-triazole linkages between monomers through an improved copper-catalyzed azide–alkyne cycloaddition (CuAAC) and a newly-optimized ruthenium-catalyzed azide–alkyne cycloaddition (RuAAC), respectively. Improvements to the Flow-IEG framework enabled the library synthesis of monodisperse oligomers with variations in triazole connectivity. These discrete oligomers allowed the systematic evaluation of the consequences of triazole sequence on material properties. The crystallization properties of these macromolecules were highly dependent on both their monomer sequence and triazole substitution pattern.