title: Development of a Method for the N-Arylation of Amino Acid Esters with Aryl Triflates.
abstract: A general method for the N-arylation of amino acid esters with aryl triflates is described. Both α- and β-amino acid esters, including methyl, tert-butyl, and benzyl esters, are viable substrates. Reaction optimization was carried out by design of experiment (DOE) analysis using JMP software. The mild reaction conditions, which use t-BuBrettPhos Pd G3 or G4 precatalyst, result in minimal racemization of the amino acid ester. This method is the first synthetic application of the t-BuBrettPhos Pd G4 precatalyst. Mechanistic studies show that the observed erosion in enantiomeric excess is due to racemization of the amino acid ester starting material and not of the product.
authors: Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors: Sandra M
authors: SM
authors: King
authors: Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors: Stephen L
authors: SL
authors: Buchwald
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D004952:Esters / Q000737:chemistry*; D008698:Mesylates / Q000737:chemistry*; D008968:Molecular Conformation
chemical_list: D000596:Amino Acids; D004952:Esters; D008698:Mesylates; C012077:trifluoromethanesulfonic acid