This Is AuburnElectronic Theses and Dissertations

A Non-Cross-Coupling-Based Approach to Arene-Bridged Macrocycles and Their Use in the Development of Annulative Pi-Extension Methods




Mitra, Nirmal Kumar

Type of Degree

PhD Dissertation


Chemistry and Biochemistry


The synthesis of strained macrocyclic benzene-containing molecules has been an area of interest for decades. However, the synthesis of macrocyclic structures that contain adjacent benzene units linked at their 1 and 4 positions (i.e., a para-phenylene unit) has presented a challenge for chemical synthesis. Chemical reactions that are well suited for the formation of biaryl bonds typically fail when called upon to furnish macrocyclic (biaryl-containing) systems. This dissertation deals with the development of a synthetic strategy that avoids the use of venerable biaryl bond-forming reactions, which in turn, has led to the synthesis of regioselectively functionalized biaryl-containing macrocyclic, benzenoid systems. Chapter 1: A non-cross-coupling-based approach to arene-bridged macrocycles has been described. This strategy involves the conversion of an unstrained 1,4-diketo-bridging unit into strained para-phenylene unit. The final macrocyclic target contains a bent p-terphenyl unit, which can be viewed as a substructure of an [n]CPP. Regioselective bromination of the p-terphenyl unit represents a rare example where such a nanostructure can be selectively derivatized. Chapter 2: The synthesis of homologous series of macrocyclic 1,4-diketones using an optimized three-step reaction protocol has been developed. This streamlined approach affords gram-scale quantities of these 1,4-ketones, which were later converted into a series of highly strained para-phenylene-bridged macrocycles. During these investigations, strain-induced rearrangement reactions were encountered during the aromatization of macrocyclic cyclohex-2-ene-1,4-diol units. This was overcome by developing a mild dehydrative aromatization protocol, which employed the Burgess reagent. The application of this macrocyclic 1,4-diketone-based approach to highly strained para-phenylene units culminated with the synthesis of macrocyclic system that contains a benzene ring more strained than a monomer unit of [4]CPP. Chapter 3: An overview of annulative pi-extension (APEX) methods for the synthesis of polycyclic aromatic hydrocarbons (PAHs) is described. A detailed investigation of an oxidative aryl coupling reaction, known as the Scholl, and its application towards APEX of a series of selectively arylated, strained p-terphenyl-containing macrocycles is reported. The development of an APEX strategy that involves allylic arylation of selectively functionalized cyclohex-2-ene-1,4-diols is described, as well as reaction mechanisms that explain observed rearrangement reactions.