Amide-derived enols in enol–Ugi reactions: expanding horizons for peptidomimetic scaffold synthesis

Abstract

A highly efficient enol–Ugi reaction of β,β-diketoamides has been developed using a novel non-heterocyclic amide-stabilised enol. This approach enables a broad reaction scope, affording β-enaminoamide peptidomimetics with constrained conformations due to CH–π interaction and C(sp³)H⋯O hydrogen bonding. Notably, the use of a five-membered cyclic enol is crucial for achieving stable products in excellent yields. This work highlights the potential of the enol–Ugi reaction for constructing diverse peptidomimetic scaffolds.