Synthesis of 1,5-diazaspiro[2.3]hexanes, a novel diazaspirocyclic system

The convenient synthesis of 1,5-diazaspiro[2.3]hexanes, as new structurally challenging strained diazaspirocyclic compounds, was developed starting from easily accessible ethyl 2-(bromomethyl)-1-tosylaziridine-2-carboxylate. The key transformations in the developed four-step sequence involved a chemoselective reduction of the functionalized ethyl 1-tosylaziridine-2-carboxylate to the corresponding β-bromo aldehyde and an aza-Payne-type rearrangement of intermediate N-tosyl 2-(aminomethyl)aziridines into N-alkyl 2-(aminomethyl)aziridines. A final base-mediated cyclization of the formed bromo amines gave efficient access to the new diazaspirocyclic system.