Synthesis of Enantiopure 1,2-Diaminobicyclo[2.2.2]octane Derivatives, <i>C</i>₁‑Symmetric Chiral 1,2-Diamines with a Rigid Bicyclic Backbone

The synthesis of enantiopure 1,2-diaminobicyclo[2.2.2]­octane (DABO, <b>1</b>) and its two selectively <i>N</i>-Boc monoprotected derivatives <b>15</b> and <b>16</b> is described. Starting from bicyclic β-amino acid <b>3</b> or <b>5</b>, strategies involving Curtius and Hofmann rearrangements were explored, demonstrating the unprecedented influence of the bicyclic backbone unsaturation for the preparation of the corresponding diamines that could be only obtained in good yield using the Hofmann rearrangement of unsaturated compound <b>3</b>. The divergent outcome observed during the Hofmann rearrangement of <b>3</b> and <b>5</b> was investigated by DFT calculations