Efficient Synthesis of Sequence-Defined Oligomers through Orthogonal CuAAC and IrAAC Reactions

Abiotic sequence-defined polymers hold tremendous promise for applications in nanotechnology, materials science, biomedicine, and data storage. Yet, their synthesis often demands complex, iterative procedures involving multiple deprotection or activation steps. To address this challenge, we present a highly efficient “AB + AC” orthogonal coupling strategy that integrates copper-catalyzed azide–alkyne cycloaddition (CuAAC) and iridium-catalyzed AAC (IrAAC). This approach leverages the exceptional chemoselectivity of each reaction to construct sequence-defined oligotriazoles without the need for protecting groups. Notably, by employing distinct terminal alkyne and thioalkyne substrates, our method enables precise, stepwise elongation of macromolecular chains on a gram scale, even when incorporating diverse functional monomers, underscoring its practicality for large-scale applications. Comprehensive analyses via size exclusion chromatography, mass spectrometry, and nuclear magnetic resonance techniques confirm the high purity and structural accuracy of the resulting oligomers. Moreover, the clear fragmentation patterns observed in tandem mass spectrometry (MS/MS) highlight the suitability of these triazole-rich architectures for high-fidelity data encoding, thereby paving the way for advanced applications in high-density information storage. Overall, this work not only expands the synthetic toolbox for creating precision polymers but also offers a robust platform for the development of next-generation materials with tunable properties and broad technological relevance.