Ligand-enabled β-C-H arylation of α-amino acids using a simple and practical auxiliary

J Am Chem Soc. 2015 Mar 11;137(9):3338-51. doi: 10.1021/ja512690x. Epub 2015 Mar 3.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / chemistry
  • Amino Acids / chemical synthesis
  • Amino Acids / chemistry*
  • Carboxylic Acids / chemistry
  • Catalysis
  • Chemistry Techniques, Synthetic
  • Hydrogen / chemistry
  • Ligands
  • Palladium / chemistry
  • Phenylalanine / chemistry
  • Pyridines

Substances

  • Amino Acids
  • Carboxylic Acids
  • Ligands
  • Pyridines
  • Phenylalanine
  • Palladium
  • Hydrogen
  • pyridine
  • Alanine