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

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journal contribution
posted on 11.03.2015, 00:00 authored by Gang Chen, Toshihiko Shigenari, Pankaj Jain, Zhipeng Zhang, Zhong Jin, Jian He, Suhua Li, Claudio Mapelli, Michael M. Miller, Michael A. Poss, Paul M. Scola, Kap-Sun Yeung, Jin-Quan Yu
Pd-catalyzed β-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 β-C–H activation, albeit this system was not compatible with carboxylic acids containing α-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 β-arylation of carboxylic acid derivatives, especially α-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.