A simple, mild and efficient synthesis of cyclopropylidene iminolactones from cyclopropanecarboxamides

Functionalized cyclopropanes are important as versatile building blocks in synthesis and as biologically active substances. However, there are only a few examples of cyclopropylidene iminolactones and their preparation involves the cyclization of γ-hydroxynitriles, limiting structural variation. Herein, we describe a two-step synthesis of novel N-substituted cyclopropylidene iminolactones 1 from γ,δ-epoxymalonate 2. Initially, epoxide 2 was treated with LiCl and an amine to produce cyclopropanecarboxamide 3 through the intermediacy of bicycliclactone 4. Triflic acid mediated protonation of benzylic hydroxyl group in 3, triggering an intramolecular SN2 attack of amidic oxygen leading to iminium salt 5, which was neutralized to furnish iminolactone 1. Phenyl group plays a pivotal role for the formation of 1 due to its stabilizing effect on the positive partial charge of benzylic carbon. In addition to the simplicity and good yields, the synthesis of cyclopropylidene iminolactones developed herein is stereoselective and amenable to functional group diversity.