Palladium-Catalyzed Site-Selective γ-C(sp3)–H Silylation of Peptides
Divergent Synthesis of Silicon-Containing Peptides via Pd-Catalyzed Post-Assembly γ-C(sp3)–H Silylation.
ACS Catal. 2019;
20 May 2019 (online)
Key wordslate-stage functionalization - peptide modification - silylation - palladium catalysis - C–H activation
Chemically modified unnatural peptides are often endowed with improved biological and pharmacokinetic properties and are therefore valuable in the drug-discovery process. Modification by silicon-containing groups appears to be promising, because the presence of a silicon moiety in amino acids or peptides can help to improve permeation through membranes and increase proteolytic stability.
Shi and co-workers have developed an efficient procedure for the synthesis of various γ-silyl-α-amino acids and oligopeptides by palladium(II)-catalyzed γ-C(sp3)–H silylation. The present site-specific late-stage C(sp3)–H functionalization is assisted by a picolinamide auxiliary and uses cheap and commercially available hexamethyldisilane as a silylating agent. Compatibility with a broad range of amino acid residues and the facile removal of the picolinamide auxiliary are noteworthy features of the present protocol.