enantiomerization

Enantiomerization is the process by which a chiral molecule interconverts between its enantiomeric forms. This interconversion can occur through inversion of a stereogenic center, through conformational changes that effectively invert chirality, or through more restricted processes such as atropisomerization (restricted rotation about a bond). The rate of enantiomerization depends on the activation barrier separating the two configurations: low barriers yield rapid interconversion and racemization at ambient conditions, while high barriers yield persistent, single-handed forms.

Mechanisms of enantiomerization vary with the molecular framework. In molecules with stereogenic nitrogen atoms, pyramidal inversion can rapidly interconvert enantiomers. For carbon-centered stereocenters, interconversion may involve bond-breaking or rearrangement steps that pass through higher-energy, less-chiral transition states. In atropisomeric systems, enantiomerization requires overcoming the barrier to rotate around a hindered bond, leading to temperature-dependent dynamics.

Enantiomerization is a key consideration in many fields. In pharmaceuticals, it can erode optical purity of chiral drugs or catalysts if uncontrolled. In dynamic stereochemistry, deliberate enantiomerization under controlled conditions enables studies of racemization rates, dynamic kinetic resolution, or the operation of chiral switches. Analysts measure enantiomerization rates by monitoring the enantiomeric excess over time using chiral chromatography or spectroscopic methods, and relate them to rate constants and activation energies via Arrhenius-type analyses.