Ambient temperature synthesis of high enantiopurity N-protected peptidyl ketones by peptidyl thiol ester-boronic acid cross-coupling.
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.
Yang
Hao
H
Department of Chemistry, Emory University, 1515 Dickey Drive NE, Atlanta, Georgia 30322, USA.
Li
Hao
H
Wittenberg
Rüdiger
R
Egi
Masahiro
M
Huang
Wenwei
W
Liebeskind
Lanny S
LS
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
D001897:Boronic Acids; D003432:Cross-Linking Reagents; D004952:Esters; D007659:Ketones; D008024:Ligands; D010455:Peptides; D017905:Phosphites; D013438:Sulfhydryl Compounds; D010165:Palladium