Ball-Milling Organocatalysis

Significance

The first application of the ball-milling technology in solvent-free asymmetric organocatalysis is reported. The authors have chosen the quinidine-mediated desymmetrization of meso-anhydrides as a test reaction. The resulting hemi­esters are obtained in high yields and with moderate enantioselectivities. Under the same ball-milling conditions, a proline-catalyzed aldol reaction has been conducted, giving anti-aldol products with moderate to high diastereo-, as well as with good to excellent enantioselectivities after short reaction times. In both cases, the results compare well with those of similar reactions performed in solution at ambient temperature. A comparative study using conventional magnetic stirring could demonstrate the beneficial effect of ball milling.