Date of Award

Fall 2011

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Chemistry

First Advisor

Patrick J. Walsh

Abstract

Polyarylmethanes are an extremely valuable molecular scaffold used in fields ranging from materials chemistry to medicinal chemistry. They are found in dyes and semiconductor dopants and in drugs and drug precursors that address a variety of ailments ranging form depression and allergies to cancer and vascular disease. However, general, selective methods to synthesize polyarylmethanes are still limited. This dissertation describes some of the exploratory work done to outline the synthetic possibilities of deprotonated tricarbonylchromium-stabilized benzylic arenes in the context of selective bond-forming reactions to form polyarylmethanes. Various η6-arene-tricarbonylchromium complexes are deprotonated with the mild silamide base LiN(SiMe3)2 and used directly in selective palladium-catalyzed syntheses of polyarylmethanes and other potentially valuable molecules from aryl bromides, aryl triflates, and vinyl triflates as coupling partners. In the first chapter, we illustrate the unique aspects of tricarbonylchromium activation, such as the ability to activate not just one C–H bond, but up to six in one flask, leading to highly substituted and sterically hindered products not accessible through traditional methods. Additionally, the sterically bulky nature of the tricarbonylchromium group is exploited to direct chemistry to the opposite face of polycyclic systems, leading to stereoselective reactions difficult to achieve selectively by other methods. Compatibility with α-heteroatom substitution and β-hydrogens is also demonstrated. Finally, an unusual mode of isomerization during the cross-coupling processes is explored. In the second chapter, the methodology for the synthesis of polyarylmethanes is expanded to asymmetric syntheses of di- and tri-arylmethane complexes. Low-barrier high-throughput experimentation (HTE) methodology is successfully implemented in the search for a highly selective ligand to achieve asymmetric cross-coupling. Medicinally valuable diarylmetheylamines are obtained from tricarbonylchromium-coordinated tertiary benzylamines in good to excellent enantiomeric excess. Finally, in the third chapter we use the products of the asymmetric cross-coupling with benzylamines to introduce novel methods to synthesize a new modular chiral P∧N ligand scaffold using a unimetal super-base. These ligands may be effective in future cross-coupling reactions and asymmetric catalysis.

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