A Highly Efficient Asymmetric Organocatalytic Aldol Reaction in a Ball Mill

Anti‐aldol products with up to >99 % enantiomeric excess (ee) have been obtained by proline catalysis in excellent yields under experimentally simple solvent‐free conditions. Efficient mixing of all the components is accomplished by applying a mechanochemical technique (ball milling). The catalysis is air and moisture tolerant and can be performed with non‐purified starting materials. Even mixtures of solely solid compounds react, giving (mostly solid) products through a partially homogeneous (honey‐like) intermediate melt. Since the reactant ratio is almost 1:1 (avoiding the common excess of ketone), the product isolation is easy leading to high aldol product yields. Organocatalysis in a ball mill: Under experimentally simple solvent‐free conditions in a ball mill, anti‐aldol products with up to >99 % enantiomeric excess (ee) are formed (see scheme). The effects of concentration, water and impurities on the reaction outcome are also discussed.