Ligand-enabled palladium-catalysed enantioselective synthesis of α-quaternary amino and glycolic acids derivatives

α-Quaternary amino and glycolic acids have found application in many biologically relevant compounds and pharmaceuticals. For example, α-quaternary amino acids can act as modifiers of peptide conformation, compared with natural amino acids. Although there are numerous enantioselective methods for the synthesis of α-quaternary amino and glycolic acids through α-alkylation, α-arylation routes are challenging. Here we report two protocols for the enantioselective synthesis of chiral α-aryl quaternary amino acids and glycolic acids derivatives, respectively, using palladium catalysis with two unique sulfinamide phosphine (Sadphos) ligands. The methods employ two common heterocycles, azlactones and 5H-oxazol-4-ones, as amino acid and glycolic acid precursors and show a broad substrate scope, with high yields and excellent enantioselectivity. Density functional theory calculations of the transition-state structures, studying non-covalent interactions and using natural bond orbital analysis, reveal that C–H···O interactions between the ligand and the substrate play a critical role in the efficient stereocontrol.