Separation of the Thorpe-Ingold and Reactive Rotamer Effect by Using the Formation of Bicyclic Aziridinium Ions

The geminal dialkyl effect is widely used in organic synthesis to promote cyclization reactions, although the exact origin of its rate enhancement remains unclear. In the present study, we demonstrate the applicability of this effect for the intramolecular formation of bicyclic aziridinium ions and assign it to angle contractions provided by introduction of sterically demanding substituents. Due to the cyclic structure of the examined 3-chloropiperidines the acceleration of this ring closure cannot be explained by an increased population of reactive gauche rotamers and therefore agrees with the original Thorpe-Ingold theory. Furthermore, introduction of strained aliphatic rings resulted in internal angle expansions and were accompanied by a preliminary decrease of rate constants for the investigated aziridinium ion formation. These results lead to a linear correlation between internal angle and relative reaction rate, supported by computational and X-ray crystallographic structural data.