Date of Award
Spring 2024
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Chemistry
First Advisor
Dian Wang
Abstract
Functionalized arenes and heteroarenes are ubiquitous motifs in natural products, pharmaceuticals, and functional materials. As such, methods to place multiple functionalities on (hetero)arenes in one synthetic step create molecular complexity quickly and are highly valued. The vast majority of current strategies are metal-mediated, although others such as utilizing aryne intermediates and cycloadditions have also been reported. The premier challenge in this research area is the difficulty in controlling regioselectivity. Strategies of controlling regioselectivity have included tuning the electronic nature of the substrate, the use of directing groups (DGs), steric influences, ligand control, and photochemically initiated methods. Certain strategies tend to bias particular regioselectivity outcomes. The use of direction groups in difunctionalization, for example, tend to give ortho/ortho selectivity due to the proximity of the C-H bond to the directing group. Some advancements have emerged in expanding the scope of particular regioselectivity patterns, but many challenges still exist in this relatively underdeveloped area. Our research aims to develop difunctionalization protocols of high synthetic utility using both photochemical and ligand influences to effect uncommon selectivity patterns without the need for excessive prefunctionalization of the substrate. Our model system and proof-of-concept used [Ir(ppy)2(Cl)2]PF6 as a substrate, with the goal of difunctionalizing and isolating the coordinated phenylpyridine ligand. A mixed electrophile method combining diphenyl disulfide and N-chlorosuccinimide was used, which we hypothesized may add to the phenylpyridine ligands of the iridium complex with useful regioselectivity patterns. Visibile light (390 nm) was used to generate reactive thiophenyl and chloryl radicals which we hypothesized could difunctionalize the phenylpyridine ligand through a tandem SRAr-reductive elimination sequence. Mass spectrometry (ESI) evidence showed significant amounts of several organic products including dithiolated, thiolated plus chlorinated, and dithiolated plus chlorinated phenylpyridine products. Isolation of the products proved difficult and was ultimately unsuccessful. Further isolation techniques will be needed to isolate and fully characterize these compounds. Another reaction developed towards difunctionalization of (hetero)arenes uses Co(bpy)2Cl2 combined with activated zinc powder, a supporting N-donor ligand, an aryl bromide, DMF, and visible light irradiation (390 nm) to yield 6-phenyl – 2,2 – bipyridine. This method gives the product as the sole regioisomer. The reaction protocol provides a new aryl radical generation method that is both convenient and mild. Further optimization is needed to improve yields and expand the scope of this initial step. We envision that a rollover cyclometallation and reductive elimination sequence could give a difunctionalized bipyridine product with reliable regioselectivity.