The self-disproportionation of enantiomers (SDE) via column chromatography of β-amino-α,α-difluorophosphonic acid derivatives

This work presents the first study of the self-disproportionation of enantiomers via chromatography (SDEvC) of beta-aminophosphonic acid esters, several of which have been synthesized for the first time. Three types of structures were examined, N-acetylated, dipeptide construction with N-Cbz glycine, and a free amine. In the latter case, this is the first time that SDEvC has been reported for free amine amino acids. In all the three types of structures, significant SDE magnitudes (Delta ee's up to 55%) were exhibited underscoring the ubiquitous nature of the SDE phenomenon. Chemical models of homo- versus heterochiral intermolecular interactions are proposed to rationalize the SDE magnitude differences amongst these new beta-aminophosphonic acid derivatives. In addition, the incorporation of additional, competing binding modes to a molecule, was found to lead to a reduction of the SDE magnitude by shifting the intermolecular binding away from the stereogenic center and/or by leading to a convoluted binding system that disrupts the structured and relatively stable assemblies that give rise to the SDE.