UC Santa Barbara

Quaternary carbon stereocenters are common in complex natural products. Due in part to their stereo definition, these quaternary centers play a significant role in the biological activity of molecules thus making them attractive synthetic motifs. The asymmetric construction of these stereocenters in acyclic systems is, however, particularly difficult. Therefore, the exploration of new synthetic methods to produce quaternary centers offers access to complex natural products and the opportunity to improve current methods. Practical and efficient methods for the construction of quaternary centers inspires the development of novel synthetic strategies which are useful for the synthesis of new pharmaceuticals and organic compounds for research. The first part of this dissertation investigates the stereoselectivity of the Ireland-Claisen rearrangement with -fluoro esters. Specifically, this study shows that high diastereoselectivity and enantioselectivity can be obtained with -fluoro esters. The second part describes the development of an enantioselective alkylation reaction enabled by chiral lithium amides (CLAs). CLAs allow for the practical and rapid construction of -alkynyl acids with quaternary centers at the -position. Crystallographic studies revealed the formation of an alkynyl enediolate lithium aggregate which is responsible for enantiocontrol. The applicability of this method was demonstrated in the total synthesis of (+)-goniomitine. The final part describes the efforts towards the total synthesis of heterodimeric alkaloids, bousigonine A and bisleuconothine A. The asymmetric alkylation of -alkynyl acids with CLAs is a featured method for the stereoselective installation of the quaternary stereocenters present in both heterodimeric bisindole alkaloids and their monomeric constituents.