Postpolymerization Amidation of Discrete Oligo( <i>N</i> -succinimidyl acrylates) Enables Diversification of Discrete and Stereochemically Defined Oligoacrylamides

The preparation of discrete and stereochemically defined polymers is essential for establishing reliable structure–function relationships and enabling the rational design of functional synthetic macromolecules. Discrete oligomers with precisely defined molar mass and sequence can be accessed by combining controlled polymerization with purification; however, the functional diversity of such oligomers remains limited, because both polymerization and high-resolution separation are typically compatible only with selected functionalities. Herein, we report a versatile route to discrete oligoacrylamides bearing diverse functional groups via postpolymerization amidation of discrete oligo( N -succinimidyl acrylates) (oligo(NSA)) as common activated-ester precursors. Discrete di-, tri-, and tetra-NSA were prepared on a subgram scale by reversible addition–fragmentation chain-transfer (RAFT) polymerization followed by normal-phase flash chromatography and subsequently converted into 16 discrete oligoacrylamides bearing seven different functional groups. As an additional demonstration of stereochemical control, all four stereoisomers of di(NSA) were isolated by chiral chromatography and transformed to the corresponding stereochemically defined acrylamide dimers. This postpolymerization diversification strategy expands the structural diversity accessible for discrete oligomers and provides a practical platform for constructing well-defined oligomer libraries for downstream molecular design.