2023-01-11
Chiral Amplification through the Interplay of Racemizing Conditions and Asymmetric Crystal Growth
Publication
Publication
J. Am. Chem. Soc. , Volume 145 - Issue 1 p. 436- 442
Amplification of enantiomeric excesses (ee) is routinely observed during chiral crystallization of conglomerate crystals for which the enantiomers undergo racemization in solution. Although routes comprising a combination of crystal growth and dissolution are frequently used to obtain enantiopure molecules, crystal growth by itself has rather been considered as a source of enantiomeric erosion and discounted as a potential source of enantiomeric amplification. Counterintuitively, we here demonstrate striking enantiomeric amplification during crystal growth for clopidogrel and tert-leucine precursors. Based on a mechanistic framework, we identify that the interplay between racemization and crystal growth rates elicits this surprising effect. The asymmetric amplification of the solid-phase ee can be enhanced by increasing the mass of grown material relative to the product such that small amounts of seeds of only 60% ee already result in virtually exclusive growth of the majority phase. These results impact our understanding of asymmetric amplification mechanisms during crystallization and offer a tangible basis for practical production of enantiopure molecules.
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| , , , | |
| ACS | |
| The Netherlands Organisation for Scientific Research (NWO) | |
| doi.org/10.1021/jacs.2c10584 | |
| J. Am. Chem. Soc. | |
| Organisation | Self-Organizing Matter |
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van Dongen, S., Ahlal, I., Leeman, M., Kaptein, B., Kellogg, R., Baglai, I., & Noorduin, W. (2023). Chiral Amplification through the Interplay of Racemizing Conditions and Asymmetric Crystal Growth. J. Am. Chem. Soc., 145(1), 436–442. doi:10.1021/jacs.2c10584 |
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