Crystallisation Based Deracemisation and Chiral Resolution of Small Molecules

Enantiomeric separation of chiral molecules is pivotal for exploring fundamental questions about life's origin and various other scientific domains. Crystallisation is an important platform for the separation of chiral molecules, elegantly applied to many systems, for instance, the formation of conglomerates, where the enantiomers crystallise as separate phases. Many approaches have been proposed to explore crystallisation-driven enantiomeric separation with fewer insights into the complex pathways associated with the separation processes. Controlling derecemisation or chiral resolution through crystallisation by applying mechanical forces, magnetic substrates, and seeds have attracted significant attention due to better outcomes. Despite these advancements, the mechanisms behind the separation of enantiomers using crystallisation as a tool, especially the delicate balance between kinetically and thermodynamically controlled pathways, are unclear, particularly for small organic molecules critical to pharmaceutical applications. This review aims to address many of these challenges, providing synthetic chemists with a deeper understanding of the role of crystallisation for innovative enantiomeric separation strategies.