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.