2020 Theses Doctoral

Expanding Silane-Mediated Coupling Methodologies for the Formation of Medicinally Relevant Structural Motifs

Hughes, Isaac

A major focus of the Leighton group has been the development of efficient, scalable and step-economical reactions towards our goal of expanding the structural variants of medicinally relevant non-aromatic polyketide natural products. Over the last few years the Leighton group has developed a novel mode of strained-silane Lewis acid activation with the use of weakly-coordinating anionic catalysts. Hyper-coordinate silicates with unprecedented levels of reactivity have facilitated previously unattainable late stage complex fragment couplings. A novel method of chiral anion catalyzed nucleophilic addition to α- and β-diketones has been explored. Finally, an operationally straightforward, efficient and direct β-ketoaldehyde allylation methodology will be discussed.