Abstract
This dissertation describes the development of two synthetic methods based on alumina and dimethylsulfoxide. Chapter 1 describes the 1,2-regioselective reduction of α,β-unsaturated ketones to their corresponding allylic alcohols with NaBH4 in the presence of acidic activated alumina rehydrated to the Brockmann II grade by adding 3% w/w water. The substrate scope includes eight ketones reduced in high regio- and diastereoselectivity to their corresponding allylic alcohols. This is a first application of the general strategy of systematically tuning the surface chemistry of alumina via partial rehydration in order to modulate selectivity in a chemical reaction.
Chapter 2 describes a unique synthesis of aryl methyl sulfides via reduction of dimethylsulfoxide to dimethylsulfide at elevated temperature in the presence of Hunig’s base followed by nucleophilic aromatic substitution and demethylation. In this reaction, dimethylsulfoxide serves as a simple and inexpensive formal source of the thiomethyl moiety. Activated aryl fluorides, chlorides, and nitrobenzenes are all suitable substrates with twelve examples demonstrated.
Chapter 3 gives an account of progress made in the effort to develop an efficient synthesis of the methicillin-resistant staphylococcus aureus (MSRA)-active antibiotic tetarimycin A. The chapter describes our failed efforts to prepare a key intermediate that would potentially enable a powerful new cyclization reaction that we envisioned could generate the two central rings of the tetracyclic target via combined Knoevenagel and Friedel-Crafts transformations.