The major goal of this proposal is to develop and assay a number of chiral, non-racemic, C3-symmetrical Lewis acid catalysts. In the search for stereospecific syntheses of drug candidates, the design and development of chiral molecular enzymes to promote asymmetric synthesis is one of the premier challenges in organic chemistry. While many catalysts are generated for specific reactions, a chiral catalyst that will influence a wide range of processes is ultimately the goal. Of these chiral Lewis acid catalysts, some of the more successful ones have C2- symmetry. However, of the numerous chiral catalysts which have been developed in the past 15 years, few have had C3-symmetry, although there are numerous potential advantages. The proposed methods will establish one of the first exploratory (synthesis, evaluation, and utilization) programs towards C3-symmetrical Lewis acid catalysts.
The specific aims of this study are threefold: i) design chiral C3-symmetric Lewis acid catalysts from Kemp's triacid; ii) employ these chiral Lewis acids in various asymmetric reactions such as the Diels-Alder, Mukiyama Aldol, and Ene reactions to determine their synthetic value; iii) describe the mode of action of these catalysts, and assay methods to maximize their stereocontrol. Once the efficacy of these catalysts are established, unexplored transformations will be investigated.
