Part I: Use of quantitative structure selectivity relationships (QSSR) to predict the selectivity of new beta-aminoalcohols in the addition of diethyl zinc to benzaldehyde. Part II: Use of functionality mapping (FUNMAP) and database mining techniques (CAV

Part I. The difference between diastereomeric transition states can be calculated via modern computational methods to explain the selectivity observed in certain reactions.* However, calculation of transition states is time consuming. To get around this, it was thought that Quantitative Structure Activity Relationships (QSAR), which are used in the pharmaceutical industry, could be used to correlate the ground states of catalysts with their selectivity in an asymmetric reaction. These Quantitative Structure Selectivity Relationships (QSSR) could then be used to predict the selectivity of novel catalysts.; As a proof of principle, the addition of Et2Zn to benzaldehyde catalyzed by beta-aminoalcohols was chosen for initial studies.* A valid QSSR model was found to correlate the ground state dimer structures of known beta-aminoalcohols with their selectivities in the above reaction. New ligands were then constructed and their selectivities in the Et2Zn addition to benzaldehyde were predicted. These ligands were then synthesized and tested to discover that there was a high degree of predictive power in this QSSR method. This research also led to the discovery of two new beta-aminoalcohols (shown below) that perform the Et2Zn addition to PhCHO with very high selectivity.*; Part II. The Claisen rearrangement was discovered by Ludwig von Claisen in 1912 and is shown below.* While the Claisen rearrangement has found numerous uses in organic synthesis, catalytic, enantioselective versions have remained elusive with only two examples to date.*; It was hypothesized that one could utilize catalytic amounts of a chiral hydrogen bond donor to perform an organocatalytic, enantioselective Claisen rearrangement. The proper ligand scaffold in the form of a bis-amidinium ion was identified via a functionality mapping (FUNMAP) and database mining (via the CAVEAT program) computational protocols developed in the Kozlowski labs. The bis-amidinium ion was then used in catalytic amounts to perform an enantioselective Claisen rearrangement of an allyl vinyl ether with a trifluoromethyl group in the C2-position.* Attempts were made to increase the enantioselectivity of the above reaction by changing temperature, concentration, solvent, and water content of the reaction, but these efforts were unsuccessful. However, the modest success achieved does warrant further research.; *Please refer to dissertation for diagrams.