Leveraging Reagent/Catalyst Cooperativity in Chiral-Anion Phase Transfer Catalysis for Regio-, Diastereo-, and Enantioselective Bromination Reactions
- Miller, Edward
- Advisor(s): Toste, F. Dean
Abstract
Chapter 1 – An overview of the field of ion-pairing and phase transfer catalysis with chiral anions. Discussion and commentary in this chapter is focused on mechanistic details that led to key developments in the field, as well as future directions for areas of research.
Chapter 2 – A regio- and enantioselective bromocyclization of difluoroalkenes to access CF2Br-containing stereocenters was developed. These bromodifluoromethylated heterocycles were derivatized to a number of pharmaceutically relevant difluoromethylene-containing motifs. Additionally, an efavirenz analogue was synthesized, demonstrating the synthetic utility of this methodology. A combination of parameterization and traditional physical organic techniques was used to study the effect of the achiral bromination reagent on the regio- and enantioselectivity of the reaction.
Chapter 3 – An atropselective bromination of scalemic phenols was developed to access brominated compounds with two chiral axes via parallel kinetic resolution. The efficiency of parallel kinetic resolution was explored by using racemic starting materials, whereby one diastereomer of product was obtained in high enantioselectivity.
Chapter 4 – Preliminary reactivity was established for the chlorotetrafluorosulfanylation of aryl boron reagents, which serve as valuable intermediates en route to Ar–SF5 compounds.
Appendix – An automated process for predicting sulfimine stabilities was developed, with applications towards the identification of promising oxaziridines for methionine bioconjugation.