Ligand-Enabled β-C-H Arylation of α-Amino Acids Using a Simple and Practical Auxiliary

Pd-catalyzed beta-C-H functionalizations of carboxylic acid derivatives using an auxiliary as a directing group have been extensively explored in the past decade. In comparison to the most widely used auxiliaries in asymmetric synthesis, the simplicity and practicality of the auxiliaries developed for C-H activation remains to be improved. We previously developed a simple N-methoxyamide auxiliary to direct beta-C-H activation, albeit this system was not compatible with carboxylic acids containing alpha-hydrogen atoms. Herein we report the development of a pyridine-type ligand that overcomes this limitation of the N-methoxyamide auxiliary, leading to a significant improvement of beta-arylation of carboxylic acid derivatives, especially alpha-amino acids. The arylation using this practical auxiliary is applied to the gram-scale syntheses of unnatural amino acids, bioactive molecules, and chiral bis(oxazoline) ligands.