Harnessing the Dearomatization of O-Aryl Hydroxylamines to Synthesize Highly Functionalized Cyclic Molecules (2024)

Undergraduate: Michael Eng

Faculty Advisor: Jeffrey Johnson
Department: Chemistry

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Small organic molecules play a crucial role in modern life, comprising the active ingredient in products like pharmaceuticals and agrochemicals. Increasing molecular complexity, especially by increasing the amount of saturation and by introducing rings, has been shown to improve biological activity. Therefore, methods for accessing such structures remain of paramount importance. Dearomatization is an efficient strategy for producing such densely functionalized rings from cheap, aromatic chemical precursors. An acid-promoted dearomative ortho-amino migration of O-aryl hydroxylamines that affords 2-aminocyclohexadienones is described herein. The dearomatized intermediates can be functionalized in situ (without workup) to produce alcohols, epoxides, and arylated products. The hydroxylamine starting materials can be synthesized from commercially available or readily prepared phenols.