Palladium-Catalyzed Amination of Protected Phenylalanine Iodides Using (Hetero)aryl Amines as Nucleophiles.

We report a robust palladium-catalyzed C-N cross-coupling method optimized for selective (hetero)arylation of derivatives containing p-iodophenylalanine (p-I-Phe). The utility of this approach is demonstrated by its use in late-stage modification of clinically relevant peptides in solution-phase. The method preserves the stereochemical integrity of the peptide backbone and exhibits compatibility with side-chain protecting groups. This provides a streamlined synthetic gateway to p-amino-substituted phenylalanines and peptides, expanding the chemical space accessible for peptide-based drug design.