NITROGEN-LIGATED (POLY)CATIONIC IODINE(III) REAGENTS: PLATFORMS FOR REAGENT DEVELOPMENT AND DIVERSE HETEROCYCLIC SYNTHESES

Abstract

Hypervalent iodine (HVI) reagents are easily accessed, highly tunable, mild, selective oxidants that are less toxic and more environmentally benign compared to their heavy metal counterparts. λ3-Iodanes, which possess an iodine center bound to one aryl substituent and two heteroatom ligands, have been the subject of recent interest due to their electrophilicity and hypernucleofugality. A central focus of the Wengryniuk laboratory has been the further development and application of a class of electrostatically activated (bis)cationic nitrogen-ligated HVI (N-HVI) reagents. N-HVIs feature datively bound heterocyclic ligands which results in dramatically enhanced electrophilicity and redox potentials. Despite being a highly tunable platform for reagent development, N-HVIs remain a relatively underexplored class of λ3-iodanes. This dissertation focuses on demonstrating N-HVI’s synthetic potential and developing novel variants to enhance their synthetic utility. Chapter 1 of this dissertation serves as a general background and introduction to nitrogen-ligated HVI reagents. Chapter 2 outlines our efforts in N-HVI library expansion, novel syntheses, and characterization. With a library of 33 novel N-HVIs in hand, ligand effects on N-HVI reactivity were analyzed via qualitative and quantitative methods. Chapter 3 describes our first synthetic application of N-HVIs in the development of novel oxidative rearrangements of simple and complex cyclic alcohols. This chapter describes the chemoselective ring expansion of 2° and 3° cyclic alcohols accessing medium-sized cyclic acetal products in good to excellent yields with applicability to Complexity-to-Diversity (CTD) efforts. Chapter 4 demonstrates our initial efforts toward the development of another synthetic method where the functionalized N-heterocyclic ligands of the N-HVIs can be regioselectivity incorporated into a molecule following N-HVI activation of an olefin. The pyridinium lactone salts formed from olefinic acids were isolated in excellent yields via simple trituration, supplying a synthetically useful functional handle that was easily derivatized via known methods. These four chapters summarize the current state of the research with nitrogen-ligated HVI salts, expand upon our initial publications to highlight the development of novel heterocyclic syntheses, and provide a useful guide to further explore the reactivity of these tunable reagents.