Catalytic Peptide Synthesis: Amidation of N-Hydroxyimino Esters

Abstract

A catalytic method for the formation of amide bonds was developed in which the amidation of N-hydroxyimino esters with a broad range of amino acid tert-butyl esters is promoted by a niobium catalyst in the absence of solvent. Contrary to the predominant protocol based on reagent control commonly applied to amidation reactions, this study provides insight into an approach based on substrate control. This system affords the corresponding amides in high yields in addition to being both highly atom efficient and racemization-free. An advantage of this system is shown in that the Lewis acid catalysis proceeds chemoselectively in the presence of nonactivated esters. Furthermore, the resulting amides are easily transformed into their corresponding di- and tripeptides with high diastereoselectivities under simple hydrogenation conditions.