One-pot approach for multi-step, iterative synthesis of sequence-defined oligocarbamates

High-yielding and scalable methods for iterative synthesis of sequence-defined macromolecules are a great challenge in modern polymer chemistry. Sequence-defined macromolecules are fabricated by multi-step iterative processes that involve high reagent and solvent consumption. Moreover, every consecutive step causes yield losses that result in low overall yield. Despite the envisioned valuable functions and applications of sequence -defined polymers, the synthetic limitations constitute a barrier for the exploitation of their practical potential. Here, we investigated the one-pot synthesis of oligocarbamates without the purification of intermediates. To control the monomer sequence without isolation of intermediate product at every step, we introduced a moni-toring feedback loop to fuel the exact amount of reagents to the reaction mixture, assuring full conversion of each reaction. Based on a one-pot strategy, we have developed a facile approach for the preparation of uniform oli-gocarbamates with full control of monomer order and defined stereochemistry. The great advantage of the presented methodology is the scalability of the process (demonstrated for synthesis of 50 g) and high yield (up to 95%). Oligomers obtained on a large scale can be further used as precursors for the synthesis of polymers with high molar mass. One-pot methods combined with chemoselective reactions bear the potential to overcome existing synthesis limitations and unlock the practical use of sequence-defined macromolecules. The presented concept might be further extended to different multi-step processes.