Pd(I)-catalyzed ring-opening arylation of cyclopropyl-α-aminoamides: Access to α-ketoamide peptidomimetics

We report the unprecedent Pd(I) catalyzed ring-opening arylation of cyclopropyl-α-aminoamides. This protocol allows facile access to biologically important α-ketoamide-containing oligopeptides and even more challenging peptide-natural product conjugates. Site selectivity was achieved by introduction of special unnatural amino acids, which also meets the requisite of bioorthogonal chemistry. Mechanism investigations reveals a distinct domino radical ring-opening process through Pd(I) catalysis.