Synthesis of Oligo‐Sulfonimidates by Exponential Growth via Sulfur‐Phenolate Exchange Reactions

The synthesis of sequence‐defined oligomers with a high molecular weight has remained a challenge due to the lack of effective coupling methods, reduced reactivity and/or selectivity with increasing oligomer lengths, and poor solubility of suitable reactants and/or resulting macromolecules. Contributing to overcome these limitations, a room‐temperature method for the construction of sequence‐defined oligo‐sulfonimidates via sulfur‐phenolate exchange (SuPhenEx) reactions using an exponential growth strategy is reported. This method enables the efficient and rapid synthesis of sequence‐defined oligo‐sulfonimidates, up to a 16 mer (M w = 6.5 kDa). Next, the versatility of this method is demonstrated by synthesizing a sequence‐defined tetramer with four nonrepeating building blocks, and fusing it with the 16 mer by another SuPhenEx reaction, resulting in a sequence‐defined 20 mer (66% isolated yield; M w = 8.5 kDa). To the authors' best knowledge, this is the longest S(VI)–O‐linked sequence‐defined oligomer constructed to date. Given the flexibility of the route, constantly high yields of the SuPhenEx coupling, independent of the oligomer length, and the enantiospecific nature of SuPhenEx reactions on chiral species, this approach for the synthesis of sequence‐defined oligo‐sulfonimidates paves the way for further exploring the structure‐property relationships of sequence‐defined oligomers and other S(VI)‐O‐linked materials.