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We demonstrate that a conglomerate-forming clopidogrel precursor undergoing solution phase racemization can be deracemized through cyclic solvent removal and re-addition. We establish that the combination of slow growth and fast dissolution of crystals is ideal for rapid deracemization, which we achieve by repurposing a Soxhlet apparatus to realize the slow removal and fast re-addition of solvent autonomously. [ABSTRACT FROM AUTHOR]

All biological systems are composed of molecules of a single chirality. Although many different scenarios can lead to chiral symmetry breaking, the transmission of the absolute configuration of one compound to another one remains challenging. We here demonstrate that during crystallization‐induced chiral symmetry breaking by Viedma ripening, a cascade of different and counteracting processes can occur: solid‐solution formation and dissolution inhibition favor symmetry breaking towards the same absolute configuration, while enantioselective growth inhibition favors symmetry breaking towards the opposite absolute configuration. These insights offer a new playground for controlling symmetry breaking processes that are of fundamental and practical importance. [ABSTRACT FROM AUTHOR]

An efficient deracemization method for conversion of the racemate to the desirable (R)‐enantiomer of Praziquantel has been developed by coupling incompatible racemization and crystallization processes. By a library approach, a derivative that crystallizes as a conglomerate has been identified. Racemization occurs via reversible hydrogenation over a palladium on carbon (Pd/C) packed column at 130 °C, whereas deracemization is achieved by alternating crystal growth/dissolution steps with temperature cycling between 5–15 °C. These incompatible processes are combined by means of a flow system resulting in complete deracemization of the solid phase to the desired (R)‐enantiomer (98 % ee). Such an unprecedented deracemization by a decoupled crystallization/racemization approach can readily be turned into a practical process and opens new opportunities for the development of essential enantiomerically pure building blocks that require harsh methods for racemization. [ABSTRACT FROM AUTHOR]

Viedma ripening allows the conversion of a solid state racemate into a single enantiomer. Using the gradual conversion of a metastable racemic compound into the conglomerate, the speed of deracemization for two amino acid derivatives could be considerably increased from several days to a few hours. [ABSTRACT FROM AUTHOR]

Spontaneous symmetry breaking andchiral amplification by meansof Viedma ripening by definition should result in complete deracemizationof a racemic conglomerate into either one of the enantiomers withequal probability. In practice, however, chiral impurities influenceViedma ripening and one enantiomer is obtained in preference overthe other. Here, we show that by increasing the attrition intensityduring Viedma ripening, the effect of chiral impurities is suppressedand deracemization does yield either enantiomer with equal probability.The reason for this is that the resulting smaller crystals lead tosuch a low surface density of chiral impurities that they no longerinhibit the crystal growth sufficiently to determine the chiral outcome.Furthermore, we show that even for low attrition intensities, theeffect of chiral impurities can be canceled by using the right amount(10 ppm) of chiral additives. [ABSTRACT FROM AUTHOR]