beta-N-Heterocyclic Cyclobutane Carboximides: Synthesis through a Tandem Base-Catalyzed Amidation/aza-Michael Addition Protocol and Facile Transformations

A stereoselective one-pot double derivatization of cyclobutene-1-carboxylic acid via a mild organic base catalyzed amidation/aza-Michael addition of benzo[d]oxazol-2(3H)-ones has been developed. This unprecedented tandem reaction provides access to novel beta-N-heterocyclic cyclobutane carboximide derivatives with a trans geometry. The carboximide moiety reacts smoothly with nucleophiles, allowing access to diverse derivatives of trans-beta-N-heterocyclic cyclobutanecarboxylic acid, including peptidomimetic structures.