The Thorpe-Ingold Hypothesis of Valency Deviation. Intramolecular Hydrogen Bonding in 2-Substituted Propane-1,3-diols^1,2

gem-Disubstituent Effect: Theoretical Basis and Synthetic Applications

“…In 1961, von Schleyer pointed out that often the change in bond angle observed upon substitution is too small (2-3°) to explain the large rate enhancement during cyclization. 14 For example, during the cyclization of some substituted bromobutylamines, Brown et al observed an increase in the rate up to 10 4 , as shown in Table 4. 15 From their data it is evident that both the position and the size of the gemdisubstituent have a profound effect on the rate of ring closure of the 4-bromobutylamines 4a-g to the corresponding pyrrolidines.…”

“…In 1961, von Schleyer pointed out that often the change in bond angle observed upon substitution is too small (2−3°) to explain the large rate enhancement during cyclization . For example, during the cyclization of some substituted bromobutylamines, Brown et al observed an increase in the rate up to 10 4 , as shown in Table .…”

The gem-disubstituent effect—a computational study that exposes the relevance of existing theoretical models

“…11 In this Letter, we report a computational study which tests the validity of the three theories described above. The findings of this study indicate that the main driving force for the gem-disubstituent effect in Brown's system is the strain energy that is linearly correlated with the activation energies and with the geometrical parameters (distance, r and attack angle, a).…”

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

“…Furthermore, substitution restrains the rotational entropy in the open chain precursor more than in the cyclic product, resulting in a favourable entropy of activation Δ S ≠ for the cyclization of gem ‐disubstituted compounds. Two years later, Schleyer calculated the contribution of the angle compression to the gem ‐dialkyl effect and mentioned that the small changes of the β angle cannot solely explain the experimentally observed enhancements of rate constants up to several orders of magnitude [5] . Therefore, Bruice and Pandit developed a different theory and associated the rate enhancements with an increased population of reactive gauche rotamers, which was later entitled the “reactive‐rotamer effect” [6] .…”