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

Abstract

We report a highly efficient and practical protocol for palladium-catalyzed N-quinolylcarboxamide (AQ)-directed arylation of the unactivated β-C(sp³)–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 β-methyl group of AQ-coupled phthaloyl alanine mono-selectively, providing both natural and unnatural aromatic α-amino acids. Access to these mono-arylated compounds enables subsequent AQ-directed diastereoselective C–H functionalization, allowing the preparation of various β-disubstituted aromatic α-amino acids in a programmable manner.