UC Davis

The exploitation of resident stereogenic centers to construct new stereogenic centers is a powerful strategy employed in the synthesis of complex organic molecules. Although the influence of both α- and β-stereogenic centers on the diastereoselective addition of nucleophiles to aldehydes has been thoroughly studied, analogous studies of α- and β-substituted imines are sparse. This dissertation describes the comprehensive study of how inherent asymmetry impacts diastereoselective nucleophilic additions to α- and β-chiral N-sulfonyl imines. Chapter one discusses the development of stereodivergent Lewis acid-mediated nucleophilic additions to α-chiral N-sulfonyl imines. From this study, two sets of optimized and generalizable conditions were developed, allowing access to either syn or anti diastereomeric outcomes in >95:5 diastereomeric ratios. Chapter two discusses the diastereoselective Lewis acid-mediated nucleophilic additions to β-chiral N-sulfonyl imines. These reactions typically proceed through a six-membered chelate and result in anti-products. Experimental and computational evidence lead to the construction of a generalizable stereoelectronic model that predicts for the magnitude of selectivity observed based on conformational preferences of the substrate-Lewis acid chelate. These two chapters together constitute a complete study of how 1,2 and 1,3 asymmetric induction affect diastereoselective nucleophilic additions to chiral N-sulfonyl imines.