| I. Asymmetric Induction in Heteroatom-Substituted Aldehydes. A study of asymmetric induction in the aldol reaction between substituted enolate nucleophiles and chiral α-alkoxy aldehydes is described (eq 1). The results are inconsistent with a widely accepted model for asymmetric induction. A modified model is proposed. Theoretical support for this model at the ab initio level is presented.*; An investigation of the impact of two oxygen stereocenters on aldehyde π-facial selectivity in a systematic study of the aldol reaction between methyl ketone enolates and α,β-alkoxy aldehydes is described (eq 2). The α,β-anti-configured aldehyde exhibits consistently superior diastereoselectivity relative to the α,β-syn-configured aldehyde. A model for this phenomenon is proposed. Methods for the selective construction of all possible stereotriads are identified.*; Aldol reactions of an oxygen-substituted enolate with oxygen-substituted aldehydes are described (eq 3). The two resulting vicinal oxygen stereocenters can be formed with a high degree of stereocontrol. Methods for the selective construction of several stereotetrads are identified.*; II. Total Synthesis of (+)-Casuarine. The total synthesis of the polyhydroxylated pyrrolizidine alkaloid (+)-casuarine in nine steps and 28% overall yield is described (eq 4). The single α-amino stereocenter of a serine-derived aldehyde is used to control the configuration of five additional stereocenters in two aldol reactions of oxygen-substituted enolates.*; *Please refer to dissertation for diagrams. |
