Direct access to vicinally functionalized and N-trifluoroacetylated (bicyclic)ketopiperazines using a readily affordable N-heterocyclic anhydride

Functionalized 2-piperazinones play essential roles as conformationally-constrained peptidomimetics by mimicking inverse γ-turns in peptides. Here, we describe an efficient, scalable, stereoselective, modular, and chemoselective annulation protocol between a novel N-trifluoroacetyl anhydride and several reactive partners, including lactim ethers, imidoyl chlorides, aryl aldimines, and 1,3-azadienes, leading to vicinally functionalized (bicyclic) 2-piperazinones.