title: N-Heteroarylation of chiral α-aminoesters by means of palladium-catalyzed Buchwald-Hartwig reaction.
abstract: N-Heteroaryl-α-amino acid derivatives are valuable pharmacological agents as peptidomimetics. Classical SNAr methods using acid catalysis and elevated temperatures could not be extended to various α-amino acids and fairly electrophilic heterocyclic partners. Here, we report a mild and versatile method of N-heteroarylation of chiral α-aminoesters without racemization, involving Buchwald-Hartwig conditions. It could be extended to various α-amino acids and azines. This efficient N-heteroarylation leads to (i) a chemical library of putative peptidomimetics combining diverse azaheterocycles with the chiral α-aminoesters and their corresponding derivatives (amides, alcohols, etc.) and (ii) arginine derivatives designed as NPFF receptor ligands.
authors.affiliation: Laboratoire d'Innovation Thérapeutique, UMR 7200, Faculté de Pharmacie, Université de Strasbourg, 74, route du Rhin, BP 60024, 67401 Illkirch, France.
authors.forename: Hassan
authors.initials: H
authors.lastname: Hammoud
authors.forename: Martine
authors.initials: M
authors.lastname: Schmitt
authors.forename: Emilie
authors.initials: E
authors.lastname: Blaise
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bihel
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Bourguignon
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D004952:Esters / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D004952:Esters; D010165:Palladium