Pd-Catalyzed site selective C(sp2)-H chalcogenation of amino acids and peptides using picolinamide auxiliary

Chalcogenated amino acids/peptides are recently being considered therapeutic drug candidates. This report describes a handy synthetic method for the Pd-catalyzed picolinamide directed site-selective C(sp2)-H chalcogenation of - amino acids and peptides with diaryl disulfides and diselenides reagents. A variety of -amino acids, benzylamines and phenethyl amines are chalcogenated in moderate to good yields bearing good selectivity. Importantly, this synthetic methodology provides the first late-stage peptide chalcogenation. Herein, ample substrate scopes with sensitive functionality, late-stage drug modification, various post-synthetic utilities including easy removal of directing group, and synthesis of indoline are systematically explored for the practical utility.