The tethered aminohydroxylation of allylic carbamates

Thesis



The osmium-mediated aminohydroxylation reaction is a powerful oxidation that introduces a hydroxyl group and a protected amino group in a syn relationship across an olefinic double bond. This study concerns one approach to controlling the regioselectivity of this oxidation.

Introduction I

The mechanism, scope and limitations of the aminohydroxylation reaction are discussed, with particular attention to the asymmetric version, providing a background from which the newly developed methodology has emerged.

Results and Discussion I

Development of the reaction

This section concerns the original attempts to perform the tethered aminohydroxylation reaction, and early process optimisation to maximise the yield of aminohydroxylated product produced.

Scope of the reaction

This section details the results of the TA reaction as applied to further allylic carbamates demonstrating the applicability of the reaction to other olefinic geometries. The diastereoselectivity of the reaction in cyclic and acyclic systems is reported, and a model to explain the observed results discussed. Also covered within are the syntheses of the various substrates and proof of the stereochemistry of the products.

Mechanistic investigations

Work involving attempts to isolate a catalytic intermediate from the reaction is described. A crystal structure of this intermediate is discussed.

Introduction II

The isolation and physiological properties of the antibiotic compound hygromycin A are described. Prior synthetic routes towards this compound are discussed.

Results and Discussion II

Three approaches towards the aminocyclitol unit of hygromycin A, employing the tethered aminohydroxylation reaction, are outlined. Two of these allow for potential future development and completion of the synthesis.

Authors: Johnson, P; Donohoe, T; Pete Johnson

• Publication date: 2003
• DOI: 10.5287/ora-nojdyxqdg
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Subjects: Osmium compounds; Oxidation; Alkenes