Nucleophile-Dependent Regio- and Stereoselective Ring Opening of 1-Azoniabicyclo-[3.1.0]hexane Tosylate

Mi-Kyung Ji, D. Hertsen, D.-H. Yoon, H. Eum, H. Goossens, M. Waroquier, V. Van Speybroeck, M. D'Hooghe, N. De Kimpe, H.-J. Ha
Chemistry - An Asian Journal
2014 (9), 1060-1067


1-[(1R)-(1-Phenylethyl)]-1-azoniabicyclo[3.1.0]hexane tosylate was generated as a stable bicyclic aziridinium salt from the corresponding 2-(3-hydroxypropyl)aziridine upon reaction with p-toluenesulfonyl anhydride. This bicyclic aziridinium ion was then treated with various nucleophiles including halides, azide, acetate, and cyanide in CH3CN to afford either piperidines or pyrrolidines through regio- and stereoselective ring opening, mediated by the characteristics of the applied nucleophile. On the basis of DFT calculations, ring-opening reactions under thermodynamic control yield piperidines, whereas reactions under kinetic control can yield both piperidines and pyrrolidines depending on the activation energies for both pathways.