Enantioselective synthesis of chiral amines through enzymatic resolution under solvent-free conditions with malonate as reagent for acylation

The extension of the enzymatic resolution of amines catalyzed by an immobilized lipase in combination with diethyl malonate as acyl donor towards a solvent-free process is described. In such a resolution process the resulting chiral amide was formed with both high conversion and enantioselectivity, and this solvent-free synthetic method turned out to be robust and efficient also at an elevated 50 mmol-scale reaction, leading to the desired amide with 50% conversion, in 43.5% yield and with excellent enantiomeric excess of 99% ee. This method proceeding at a short reaction time (4.5 h) opens up a perspective for future development towards a large-scale feasible process technology for the enantioselective synthesis of chiral amines.112