Palladium-catalyzed trifluoroacetate-promoted mono-arylation of the β-methyl group of alanine at room temperature: synthesis of β-arylated α-amino acids through sequential C-H functionalization

We report a highly efficient and practical protocol for palladium-catalyzed N-quinolylcarboxamide (AQ)-directed arylation of the unactivated beta-C(sp(3))-H bonds of alanine with aryl iodides at room temperature. For the first time, a broad range of easily accessible aryl iodides can be installed onto the beta-methyl group of AQ-coupled phthaloyl alanine mono-selectively, providing both natural and unnatural aromatic alpha-amino acids. Access to these mono-arylated compounds enables subsequent AQ-directed diastereoselective C-H functionalization, allowing the preparation of various beta-disubstituted aromatic alpha-amino acids in a programmable manner.