The synthesis of sequence-defined oligomers and polymers is an important contemporary research topic due to the potential for creating materials with function tailored directly into the primary structure. Sequence-defined materials...

The preparation of sequence‐defined macromolecules using cyclic sulfamidates on solid‐phase is outlined. The challenges surrounding an AB+CD approach are described with focus on understanding the formation of ring‐opened side products when using amide coupling reagents. To avoid undesired side product formation, a strategy of iterative ring‐openings of cyclic sulfamidates on solid‐phase is explored. Ring‐opening on primary and secondary amines is successfully reported, generating both linear and branched chain growth. However, attempts to selectively cleave N‐sulfate bearing sp3‐hybridized groups cannot be demonstrated, limiting the overall building block scope for this methodology. Consequently, the active ring‐opening of cyclic sulfamidates on amine‐functionalized oligo(amidoamine) backbones is successfully applied to produce sequence‐defined, N‐sulfated macromolecules.