Peptide Bond Formation of Amino Acids by Transient Masking with Silylating Reagents.

A one-pot peptide bond-forming reaction has been developed using unprotected amino acids and peptides. Two different silylating reagents, HSi[OCH(CF ₃ ) ₂ ] ₃ and MTBSTFA, are instrumental for the successful implementation of this approach, being used for the activation and transient masking of unprotected amino acids and peptides at C -termini and N -termini, respectively. Furthermore, CsF and imidazole are used as catalysts, activating HSi[OCH(CF ₃ ) ₂ ] ₃ and also accelerating chemoselective silylation. This method is versatile as it tolerates side chains that bear a range of functional groups, while providing up to >99% yields of corresponding peptides without any racemization or polymerization.