Mechanochemical Deracemization: A Sustainable Approach to Enantiopurity.

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 (e.e.) 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.