Kinetic Resolution of β-Hydroxy Carbonyl Compounds via Enantioselective Dehydration Using a Cation-Binding Catalyst: Facile Access to Enantiopure Chiral Aldols

A practical and highly enantioselective nonenzymatic kinetic resolution of racemic beta-hydroxy carbonyl (aldol) compounds through enantioselective dehydration process was developed using a cation-binding Song's oligoethylene glycol (oligoEG) catalyst with potassium fluoride (KF) as base. A wide range of racemic aldols was resolved with extremely high selectivity factors (s = up to 2393) under mild reaction conditions. This protocol is easily scalable. It provides an alternative approach for the syntheses of diverse biologically and pharmaceutically relevant chiral aldols in enantiomerically pure form. For example, racemic gingerols could participate in this kinetic resolution with superb efficiency (s > 240), affording both enantiomerically pure gingerols and corresponding shogaols simultaneously in a single step. The dramatic effectiveness of such kinetic resolution process can be ascribed to systematic cooperative hydrogen-bonding catalysis in a densely confined supramolecular chiral cage in situ generated from the chiral catalyst, substrate, and KF.