The enantioselective synthesis of biologically important molecules has emerged as an important challenge in drug design. Future developments in this area are dependent on the introduction of new methods for the stereoselective synthesis of biologically relevant functionalities. In this proposal, we describe methods for the resolution of two types of chiral molecules that can serve as building blocks for the preparation of bioactive organic compounds. Specifically, bis(oxazoline)copper compounds will be used to catalyze the enantioselective alcoholysis of activated chiral esters (eq 1). Related copper complexes will be used to catalyze the enantioselective acylation of secondary alcohols (eq 2). The enantioenriched products of these reactions will be useful for the synthesis of many biologically important compounds. These resolutions will also constitute significant advances in the field of organic methodology as, for the first time, Lewis acid catalysis will be applied to the stereoselective synthesis of a wide range of functionalized esters and alcohols.
