In situ carboxyl activation using a silatropic switch: a new approach to amide and peptide constructions

The novel reactivity of O-silylthionoesters with amine nucleophiles to generate oxoamides (rather than thioamides) is described. A straightforward first-generation trimethylsilylation protocol using bistrimethylsilylacetamide (BSA) combined with the unique reactivity of the O-silylthionoesters toward 1° and 2° amines to generate oxoamides provides the simplest means of activating a thiol acid for peptide bond formation at neutral pH. Excellent stereoretention is observed.