title: Ambient temperature synthesis of high enantiopurity N-protected peptidyl ketones by peptidyl thiol ester-boronic acid cross-coupling.
abstract: alpha-Amino acid thiol esters derived from N-protected mono-, di-, and tripeptides couple with aryl, pi-electron-rich heteroaryl, or alkenyl boronic acids in the presence of stoichiometric Cu(I) thiophene-2-carboxylate and catalytic Pd(2)(dba)(3)/triethylphosphite to generate the corresponding N-protected peptidyl ketones in good-to-excellent yields and in high enantiopurity. Triethylphosphite plays a key role as a supporting ligand by mitigating an undesired palladium-catalyzed decarbonylation-beta-elimination of the alpha-amino thiol esters. The peptidyl ketone synthesis proceeds at room temperature under nonbasic conditions and demonstrates a high tolerance to functionality.
authors.affiliation: Department of Chemistry, Emory University, 1515 Dickey Drive NE, Atlanta, Georgia 30322, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Wittenberg
authors.forename: Masahiro
authors.initials: M
authors.lastname: Egi
authors.forename: Wenwei
authors.initials: W
authors.lastname: Huang
authors.forename: Lanny S
authors.initials: LS
authors.lastname: Liebeskind
mesh_terms: D001897:Boronic Acids / Q000737:chemistry*; D002384:Catalysis; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004952:Esters / Q000737:chemistry*; D007659:Ketones / Q000138:chemical synthesis*; D008024:Ligands; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D017905:Phosphites / Q000737:chemistry; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013696:Temperature
chemical_list: D001897:Boronic Acids; D003432:Cross-Linking Reagents; D004952:Esters; D007659:Ketones; D008024:Ligands; D010455:Peptides; D017905:Phosphites; D013438:Sulfhydryl Compounds; D010165:Palladium