Carboxylate-Directed Pd-Catalyzed β-C(sp 3 )-H Arylation of N -Methyl Alanine Derivatives for Diversification of Bioactive Peptides.

This study presents a Pd(II)-catalyzed method for the β-C(sp 3 )-H arylation of N -Cbz- or N -Fmoc-protected N -methyl alanines, providing ready access to building blocks for N -methylated peptide synthesis. For this transformation, the native carboxylate was exploited as the directing group, attributing its success to the use of a monoprotected amino-pyridine ligand. Its synthetic utility was demonstrated by facile generation of nine analogues of the naturally occurring N -methylated cyclic peptide cycloaspeptide A.