Base-Promoted Dynamic Amide Exchange: Efficient Access to Isotopically Enriched Tertiary Amides

Amide isotope labeling is a crucial tool in drug discovery and development. However, current methods label the desired peptide bond in a multi-step fashion. This study presents novel strategies for amide isotope exchange through transamidation and amide metathesis. By optimizing reaction conditions and exploring substrate scope, we achieved direct labeling of both amine and carbonyl moieties without need for precursors preparation. These findings pave the way for sustainable isotope labeling technologies. Furthermore, preliminary examples of isotope-containing waste recycling demonstrate a crucial step towards a greener future for isotope chemistry.