DNA-Compatible Strecker Reaction for the Synthesis of α-Aminonitriles

We report a DNA-compatible synthesis of α-aminonitriles via the Strecker reaction. Systematic optimization of reaction conditions and evaluation of a broad range of aldehydes and aromatic amines revealed high functional-group tolerance, with 68% of the examined substrates affording ≥ 70% conversion. The transformation proceeds under mild conditions that preserve DNA integrity, enabling multicycle split-and-pool library synthesis. This method expands the repertoire of DNA-compatible multicomponent reactions and enables the incorporation of α-aminonitrile scaffolds into DEL platforms.