title: Ligand-enabled β-C-H arylation of α-amino acids using a simple and practical auxiliary.
abstract: 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.
authors.affiliation: Department of Chemistry, The Scripps Research Institute , 10550 N. Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Shigenari
authors.forename: Pankaj
authors.initials: P
authors.lastname: Jain
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Zhong
authors.initials: Z
authors.lastname: Jin
authors.forename: Jian
authors.initials: J
authors.lastname: He
authors.forename: Suhua
authors.initials: S
authors.lastname: Li
authors.forename: Claudio
authors.initials: C
authors.lastname: Mapelli
authors.forename: Michael M
authors.initials: MM
authors.lastname: Miller
authors.forename: Michael A
authors.initials: MA
authors.lastname: Poss
authors.forename: Paul M
authors.initials: PM
authors.lastname: Scola
authors.forename: Kap-Sun
authors.initials: KS
authors.lastname: Yeung
authors.forename: Jin-Quan
authors.initials: JQ
authors.lastname: Yu
mesh_terms: D000409:Alanine / Q000737:chemistry; D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry; D002384:Catalysis; D060326:Chemistry Techniques, Synthetic; D006859:Hydrogen / Q000737:chemistry; D008024:Ligands; D010165:Palladium / Q000737:chemistry; D010649:Phenylalanine / Q000737:chemistry; D011725:Pyridines
chemical_list: D000596:Amino Acids; D002264:Carboxylic Acids; D008024:Ligands; D011725:Pyridines; D010649:Phenylalanine; D010165:Palladium; D006859:Hydrogen; C023666:pyridine; D000409:Alanine