# Resolution of a Chiral β‐Aminoketone via Diastereomeric Salt Formation: From Experimental Evidence to Molecular‐Level Insights Into Solution‐Phase Clusters

## TL;DR

This paper explains how a chiral compound can be separated into its enantiomers using diastereomeric salt formation and provides molecular insights into the process.

## Contribution

The study connects experimental resolution with molecular dynamics simulations to explain enantiomeric separation at the prenucleation stage.

## Key findings

- Diastereomeric salt formation enables stereoselective precipitation of a β-aminoketone.
- Molecular simulations reveal differences in ionic cluster dynamics between homochiral and heterochiral salts.
- Chiral counterions play a crucial role in directing the selectivity of the resolution process.

## Abstract

The classical diastereomeric salt resolution approach was employed to separate (±)‐1,3‐diphenyl‐3‐(phenylamino)propan‐1‐one using both enantiomers of 10‐camphorsulfonic acid (CSA) as resolving agents. Gentle stirring at room temperature resulted in the stereoselective precipitation of a single diastereomeric salt, yielding a solid phase highly enriched in one enantiomer of the target compound. Control experiments confirmed the crucial role of the chiral counterion in directing the selectivity of the process. Molecular Dynamics simulations and subsequent Principal Component Analysis revealed slight but significant differences in the pre‐nucleation size distribution of ionic clusters and in the dynamics of their mutual interconversion, hence suggesting that these differences could play a role in the racemic resolution.

Subtle but significant differences between the heterochiral and homochiral salts during the prenucleation stage, revealed by molecular simulations, are related to the enantiomeric separation of a β‐aminoketone through the precipitation of its corresponding diastereomeric salts.