Oxime radicals: generation, properties and application in organic synthesis.

Igor B Krylov,Stanislav A Paveliev,Alexander S Budnikov,Alexander O Terent'Ev

doi:10.3762/bjoc.16.107

Abstract

N-Oxyl radicals (compounds with an N–O• fragment) represent one of the richest families of stable and persistent organic radicals with applications ranging from catalysis of selective oxidation processes and mechanistic studies to production of polymers, energy storage, magnetic materials design and spectroscopic studies of biological objects. Compared to other N-oxyl radicals, oxime radicals (or iminoxyl radicals) have been underestimated for a long time as useful intermediates for organic synthesis, despite the fact that their precursors, oximes, are extremely widespread and easily available organic compounds. Furthermore, oxime radicals are structurally exceptional. In these radicals, the N–O• fragment is connected to an organic moiety by a double bond, whereas all other classes of N-oxyl radicals contain an R2N–O• fragment with two single C–N bonds. Although oxime radicals have been known since 1964, their broad synthetic potential was not recognized until the last decade, when numerous selective reactions of oxidative cyclization, functionalization, and coupling mediated by iminoxyl radicals were discovered. This review is focused on the synthetic methods based on iminoxyl radicals developed in the last ten years and also contains some selected data on previous works regarding generation, structure, stability, and spectral properties of these N-oxyl radicals. The reactions of oxime radicals are classified into intermolecular (oxidation by oxime radicals, oxidative C–O coupling) and intramolecular. The majority of works are devoted to intramolecular reactions of oxime radicals. These reactions are classified into cyclizations involving C–H bond cleavage and cyclizations involving a double C=C bond cleavage.

Highlights

Free radicals in which an unpaired electron is localized on the N–O fragment (N-oxyl radicals, Figure 1) occupy a special place in organic chemistry due to the increased stability and ease of generation, the diversity of their structures, properties, and applications.Stable N-oxyl radicals are used in the development of organic magnetic materials [1], organic batteries [2,3,4], in the preparation of polymers by living polymerization [5,6], in the studies of biomolecules and living systems by EPR [7] and NMR [8] techniques
This review focuses on the synthetic use of oxime radicals
An unprecedented renaissance in the chemistry of oxime radicals has been observed during the last years

Summary

Introduction

Free radicals in which an unpaired electron is localized on the N–O fragment (N-oxyl radicals, Figure 1) occupy a special place in organic chemistry due to the increased stability and ease of generation, the diversity of their structures, properties, and applications. 5-endo-trig cyclization affording hydroxyisoxazoline 110’ in good yield was observed Another approach to the synthesis of hydroxy-substituted isoxazolines 113 is the manganese(III) acetylacetonate catalyzed reaction of β,γ-unsaturated oximes 112 with oxygen of air (Scheme 36) [126]. The authors showed that the initial product of the oxidative cyclization of oxime 122a under the action of TBN was the dimer 127 of the nitroso compound 126, which was formed, presumably, as a result of nitrosation of the C-centered radical 125 by TBN [130]. The authors proposed a mechanism involving a 5-exo-trig cyclization of the oxime radical followed by the addition of molecular oxygen to the formed C-centered radical with a formation of a peroxyl radical The interaction of the latter with NO leads to the final oxynitro compound [131]. The authors proposed that under ultrasonic stimulation the mechanism is predominantly radical, while under microwave conditions the ionic mechanism becomes significant [157]

Conclusion

Nitroxide Mediated Polymerization