Crystallization: A Tool for Asymmetric Synthesis and Isolation

This chapter presents crystallization-based strategies to help chemists obtain enantiopure compounds, with a focus on recent advancements and publications. Resolution-based approaches including classical diastereomeric resolution and preferential crystallization are first presented and their rational design is explained. Approaches that combine racemization and crystallization are then highlighted, including crystallization-induced diastereomer transformations, atropisomers, attrition-enhanced deracemization and temperature cycling-induced deracemization. Racemization strategies are then summarized using examples from the literature, including configurational, chiral carbon and chiral heteroatom racemization. Lastly, recent technological advances are outlined including continuous crystallization and process analytical technology, continuous preferential crystallization, physical separation of racemization and crystallization, and other promising technologies that are being applied to crystallizations.