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. 2025 Mar 12;31(15):e202404120.
doi: 10.1002/chem.202404120. Epub 2025 Jan 10.

Mechanochemical Deracemization: A Sustainable Approach to Enantiopurity

Job Gieling  1 , Guillaume Wéry  1 , Chrystal Lopes  2 , Joséphine de Meester  1 , Clément Brandel  2 , Yohann Cartigny  2 , Tom Leyssens  1 , Daniel M Baier  1
Affiliations

Mechanochemical Deracemization: A Sustainable Approach to Enantiopurity

Job Gieling et al. Chemistry. .

Abstract

We introduce mechanochemical deracemization (MCDR) as a novel strategy for obtaining enantiopure compounds. This study demonstrates the successful transposition of six archetypical deracemization reactions from a solvent-based to a solvent-minimized ball milling environment. The scope includes a ketone, isoindolinones, imines, an ester, and an inorganic compound, all of which deracemized successfully. Key parameters such as milling material, ball number and size, the use of a bulk material and liquid-assisted grinding (LAG) were systematically investigated, revealing their crucial role. Quantitative enantiomeric excesses (ee) were achieved, while reaction times were reduced by up to 97 % and solvent consumption by as much as 100 %. This work establishes MCDR as a versatile, sustainable pathway to enantiopure compounds. By highlighting the generalizability of this approach and its huge potential for minimizing waste, this study provides the foundation for future advancements in mechanochemical deracemization.

Keywords: Ball Milling; Chirality; Deracemization; Mechanochemistry; Sustainable Chemistry.

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