Journal of the American Chemical Society 2007-02-07

Ambient temperature synthesis of high enantiopurity N-protected peptidyl ketones by peptidyl thiol ester-boronic acid cross-coupling.

Hao Yang, Hao Li, Rüdiger Wittenberg, Masahiro Egi, Wenwei Huang, Lanny S Liebeskind

Index: J. Am. Chem. Soc. 129 , 1132, (2007)

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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.