Stereoselective Synthesis of cis , cis ‐Configured Vicinal Triamines

The first stereoselective synthesis of a cis , cis ‐configured vicinal triamine was achieved, starting from N ‐cyclohexenylpyrrolidone ( 10 ). The reaction sequence consists of the stereoselective construction of the trans ‐configured 1,3‐diamide 14 , trans ‐to‐ cis isomerization via enols or enamines, and subsequent highly stereoselective reduction of the intermediate imine 17D to the amine 18A . The postulated reaction pathway explains the observed stereoconvergence and is supported by calculation of the heats of formation of its intermediates at the PM3 level. LiAlH 4 reduction of 18A yielded the tetracyclic aminal 19 , which was converted into the pyrrolidinylquinoxaline 7 , which showed low to moderate affinity towards κ and σ 1 receptors.