Stable Bicyclic Functionalized Nitroxides: The Synthesis of Derivatives of Aza-nortropinone–5-Methyl-3-oxo-6,8-diazabicyclo[3.2.1]-6-octene 8-oxyls

Abstract

In recent decades, bicyclic nitroxyl radicals have caught chemists’ attention as selective catalysts for the oxidation of alcohols and amines and as additives and mediators in directed C-H oxidative transformations. In this regard, the design and development of synthetic approaches to new functional bicyclic nitroxides is a relevant and important issue. It has been reported that imidazo[1,2-b]isoxazoles formed during the condensation of acetylacetone with 2-hydroxyaminooximes having a secondary hydroxyamino group are recyclized under mild basic catalyzed conditions to 8-hydroxy-5-methyl-3-oxo-6,8-diazabicyclo[3.2.1]-6-octenes. The latter, containing a sterically hindered cyclic N-hydroxy group, upon oxidation with lead dioxide in acetone, virtually quantitatively form stable nitroxyl bicyclic radicals of a new class, which are derivatives of both 2,2,6,6-tetramethyl-4-oxopiperidine-1-oxyl (TEMPON) and 3-imidazolines.

Keywords

• bicyclic nitroxide
• condensation
• acetylacetone
• base-catalyzed recyclization
• 3-imidazoline nitroxide
• TEMPON