Divergent Synthesis of Silicon-Containing Peptides via Pd-Catalyzed Post-Assembly γ-C(sp3)-H Silylation

Silicon-containing peptides hold great promise for maintaining or enhancing biological activity, while simultaneously improving the proteolytic stability. Herein, we report the Pd(II)-catalyzed gamma-C(sp(3))-H silylation of alpha-amino acids and peptides. Quinone-type ligands play a pivotal role in this reaction, and hexamethyldisilane was used as silylation reagent. The facile removal of a picolinamide auxiliary and the compatibility with a wide range of oligopeptides bearing various a-amino acid residues render this protocol a valuable strategy to access gamma-silyl-alpha-amino acids and peptides. This reaction enriches the chemical toolbox for the site-specific peptide modification and showcases the vast potential of postsynthetic diversification of peptides via late-stage C(sp(3))-H functionalization.