In the proposed work, the feasibility of a new method for the discovery of asymmetric catalysts will be tested, employing a """"""""combinatorial"""""""" approach in which large numbers of candidates are prepared and screened. Libraries of chelating chiral, non-racemic Beta-amino and Beta-imino- alcohol ligands will be prepared in a two-step modular assembly process on solid-phase supports in high yield and high purity; surface-bound chiral Lewis acidic metal complexes will be prepared from these ligands; the effectiveness of the derived Lewis acids will be assayed under a variety of conditions as asymmetric catalysts for the key Diels-Alder reaction in a published synthesis of mitomycins A and C; and a highly effective catalyst will be developed from one or more repetitions of the above combinatorial cycle using modified ligands based upon the most successful candidates in the previous trial. A successful extension of combinatorial methods from the current growing application in the synthesis of biomolecules to the construction of chiral catalysis would most likely have a broad impact on current and future synthetic strategies.
