Developing novel 1,2-azaborine building blocks & the basic science of 1,2-azaborine as hydrogen-bond donors

Abstract

The overarching theme of this dissertation is developing 1,2-azaborine motif as a novel arene pharmacophore. The first chapter of this dissertation is about exploring the synthesis and character of a new α-boryl diazo family-diazomethyl-1,2-azaborine and its diverse reaction chemistry. As a remarkable 1,2-azaborine building block, it can undergo a variety of classical diazo reactions including C–H activation, O–H activation, [3+2] cycloaddition, halogenation, and Ru-catalyzed carbonyl olefination. In the second chapter, we take a closer look at the hydrogen bond donor ability of 1,2-azaborines. A congeneric series of 1,2-azaborine ligands were used to probe the strength of hydrogen bonding as a function of the ligand’s steric effects. The results of this study provide fundamental reference data for establishing 1,2-azaborines as potential pharmacophores. Lastly, 1,2-azborine as a new ligand for T4 lysozyme double mutant L99A/M102 was investigated, and a new mode of ligand-protein interaction was discovered and evaluated by X-ray crystallography and ITC.