title: A practical aryl unit for azlactone dynamic kinetic resolution: orthogonally protected products and a ligation-inspired coupling process.
abstract: The first strategy for bringing about enantioselective azlactone dynamic kinetic resolution to generate orthogonally protected amino acids has been developed. In the presence of a C2-symmetric squaramide-based catalyst, benzyl alcohol reacts with novel yet readily prepared tetrachloroisopropoxycarbonyl-substituted azlactones to generate trapped phthalimide products of significant synthetic interest with excellent enantiocontrol. These materials are masked amino acids which are demonstrably orthogonally protected: cleavage of the phthalimide can be achieved in the presence of the ester and vice versa. This process could be utilized to bring about a highly stereoselective ligation-type coupling of protected serines (at stoichiometric loadings) with racemic azlactones derived from both natural and abiotic amino acids. After deprotection, a subsequent base-mediated O→N acyl transfer occurs to form a dipeptide.
authors.affiliation: Trinity Biomedical Sciences Institute, School of Chemistry, The University of Dublin, Trinity College, Dublin 2 (Ireland).
authors.forename: Sean
authors.initials: S
authors.lastname: Tallon
authors.forename: Francesco
authors.initials: F
authors.lastname: Manoni
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Connon
mesh_terms: D000577:Amides / Q000737:chemistry; D019905:Benzyl Alcohol / Q000737:chemistry; D002384:Catalysis; D004952:Esters; D007700:Kinetics; D007783:Lactones / Q000737:chemistry*; D010797:Phthalimides / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000577:Amides; D004952:Esters; D007783:Lactones; D010797:Phthalimides; C037431:phthalimide; D019905:Benzyl Alcohol
keywords: amino acids; asymmetric catalysis; kinetic resolution; organocatalysis; peptides