Continuous flow enzymatic kinetic resolution and enantiomer separation using ionic liquid/supercritical carbon dioxide media

The combination of kinetic resolution in ionic liquids (IL) and selective extraction with super-critical carbon dioxide (scCO(2)) provides a new approach for the separation of enantiomers as exemplified by the lipase-catalyzed esterification of chiral secondary alcohols. Excellent enantioselectivities are achieved upon conversion of alcohols 1a-e to the corresponding acetates 4a-a or laureates 5a-e using various modifications of the lipase from Candida antarctica (CaL-B) in imidazolium-based ionic liquids. The anion of the ionic liquid has a significant influence on the performance of the bio-catalyst with bis(trifluoromethanesulfonamide) [BTA] giving the best results. The acetates 4a-a can be extracted from the reaction mixture preferentially over the alcohols 1a-a with scCO(2) under certain conditions, but preparatively useful selectivities would require advanced multi-step extraction procedures. In contrast, efficient separation is possible with relatively simple equipment if alcohols la-a are extracted preferentially from their corresponding laureates 5a-e. A "green" continuous process for the resolution of racemic alcohols without the use of organic solvents was devised on the basis of these findings.