Direct Access to α,β-Unsaturated γ-Lactams via Palladium-Catalysed Carbonylation of Propargylic Ureas

Abstract

Abstract. Additive carbonylations typically necessitate strong nucleophiles, such as alcohols or amines. In this study, we carbonylated a poorly nucleophilic urea, under oxidant-free conditions. Our straightforward carbonylative strategy enables access to versatile α,β-unsaturated γ-lactams featuring an aminocarbonyl fragment, utilizing readily available propargylic ureas as starting materials. The employment of the PdI2/KI catalytic system allowed complete regioselectivity (5-endo-dig), high functional group tolerance, broad substrate scope as well as operational simplicity (oxidant-free, organic ligand-free and base-free protocol). The synthetic utility of these γ-lactams is showcased through late-stage functionalizations, such as Giese reactions and peptide couplings.