1KeyLaboratoryofOrganicSynthesisofJiangsuProvince,CollegeofChemistry,ChemicalEngineeringandMaterials Science,SoochowUniversity, Suzhou215123,China.
a-amino acids bearing aromatic side chains are important synthetic units in the synthesis of peptides and natural products. Although various b-C-H arylation methodologies for amino acid derivatives involving the assistance of directing groups have been extensively developed,syntheses that directly employ N-protected amino acids as starting materials remain rare. Herein, we report an N-acetylglycine-enabled Pd-catalysed carboxylate-directed b-C(sp3)-H arylation of aliphatic acids. In this way, various non-natural amino acids can be directly prepared from phthaloylalanine in one step in good to excellent yields. Furthermore, a series of aliphatic acids have been shown to be amenable to this transformation, affording b-arylated propionic acid derivatives in moderate to good yields. More importantly, this ligand-enabled direct b-C(sp3)-H arylation could be easily scaled-up to 10 g under reflux conditions, highlighting the potential utility of this synthetic method.