Solvent-free asymmetric anhydride opening in a ball mill

The mechanochemical technique of ball milling has been applied to the asymmetric opening of meso-anhydrides, mediated by the cinchona alkaloid quinidine. A simple workup procedure affords the products, optically active dicarboxylic acid monoesters, in high yields, with up to 64% ee. With most substrates no column chromatography was needed. A range of various alcohols, as well as anhydrides, reacted well thus demonstrating the scope of this methodology. Even mixtures of purely solid components react, and no solvent is required ( except during the workup). The possible use of almost equimolar amounts of starting materials significantly simplifies the product isolation compared to the standard solution reaction.