Browsing by Subject "Alkene"

Nitrogen-containing compounds, specifically the 1,2-oxyamino moiety, are of vital importance to modern pharmaceuticals, natural products, and agrochemicals. 1,2-Difunctionalization of alkenes offers an efficient approach to assemble these scaffolds in a single step from readily available starting materials. In this dissertation, a novel copper-catalyzed amino oxygenation strategy of alkenes has been established using O-benzoylhydroxylamines as an electron-rich amine precursor and oxidant. First, copper-catalyzed amino lactonization was achieved starting with carboxylic acid-tethered alkenes. This intramolecular transformation is also applicable to alcohols, amides, 1,3-diones, oximes, and thioic acids as nucleophilic trapping partners. These reactions proceed in a facile manner, producing good yields and tolerance of a wide range of functional groups with excellent chemo- and regioselectivity. Mechanistic studies explicitly distinguish between a novel, electrophilic amination-initiation event and previously observed nucleophilic oxygenation-initiation events. Furthermore, the procedure can be adapted to carry out the reaction from the free amine as an O-benzoylhydroxylamine precursor. Finally, the intermolecular, three-component amino oxygenation reaction of alkenes was successfully developed using untethered carboxylic acids and O-benzoylhydroxylamines. The analogous three-component amino oxygenation reaction of dienes was also found to proceed effectively in a chemo-, regio-, and site-selective fashion.

Fluorine in modern pharmaceuticals has enabled development of drugs with enhanced therapeutic value through the selective modulation of a variety of pharmacological parameters. Therefore, methods to prepare molecular scaffolds which contain the fluorine atom are of critical importance for the continued success of novel drug discovery. In this thesis, the regioselective intermolecular aminofluorination of alkenes has been achieved with N,N-dialkylhydroxylamines and nucleophilic fluorine. With this copper-catalyzed approach, a variety of pharmaceutically relevant β-fluorophenethylamines have been prepared. Additionally, through the systematic evaluation of substituted alkenes and electronically varied O-substituted-N-hydroxylmorpholines, the limitations of the method have been discovered. Mechanistic experiments have also revealed the presence of a radical intermediate, which suggests the transformation occurs through a nitrogen-initiated pathway.