Functionalised Oximes: Emergent Precursors for Carbon-, Nitrogen- and Oxygen-Centred Radicals

Abstract

Oxime derivatives are easily made, are non-hazardous and have long shelf lives. They contain weak N-O bonds that undergo homolytic scission, on appropriate thermal or photochemical stimulus, to initially release a pair of N- and O-centred radicals. This article reviews the use of these precursors for studying the structures, reactions and kinetics of the released radicals. Two classes have been exploited for radical generation; one comprises carbonyl oximes, principally oxime esters and amides, and the second comprises oxime ethers. Both classes release an iminyl radical together with an equal amount of a second oxygen-centred radical. The O-centred radicals derived from carbonyl oximes decarboxylate giving access to a variety of carbon-centred and nitrogen-centred species. Methods developed for homolytically dissociating the oxime derivatives include UV irradiation, conventional thermal and microwave heating. Photoredox catalytic methods succeed well with specially functionalised oximes and this aspect is also reviewed. Attention is also drawn to the key contributions made by EPR spectroscopy, aided by DFT computations, in elucidating the structures and dynamics of the transient intermediates.

Keywords: EPR spectroscopy; N-heterocycles; free radicals; organic synthesis; oxime esters; oxime ethers; photochemical reactions; photoredox catalysis.

Scheme 1

Oximes, carbonyl oximes and oxime ethers; production of iminoxyl radicals.

Chart 1

Types of carbonyl oximes investigated for radical release.

Figure 1

9 GHz isotropic EPR spectra of selected iminyl radicals in t-butylbenzene solution. Left top (a) Experimental spectrum of 1-phenylpropan-2-yliminyl radical 9, with simulation below (red), during UV photolysis of dioxime oxalate 4a; Right top (b) Experimental spectrum during UV photolysis of oxime ester 3a at 320 K showing iminyl radical 11 (marked Im) in black with simulation in red (below) and double integral in green. The spectrum of adduct oxyaminyl radical 12 appears in the central region.

Scheme 2

Photolytic generation of iminyl radicals from carbonyl oximes.

Figure 2

Electronic configuration of alkyl- and aryl-iminyl radicals. (a) hyperconjugative interaction; (b) DFT computed alpha SOMO; (c) DFT computed spin density distribution.

Scheme 3

Combination, dissociation and H-atom abstraction reactions of iminyl radicals.

Scheme 4

Photo-induced oxime ester transformations [22].

Scheme 5

Reactions of designer oxime esters catalysed by fac-[Ir(ppy)₃] [51,52].

Scheme 6

Photodissociation and subsequent reactions of an oxime glyoxalate [53].

Scheme 7

Oxime oxalate amides and ring closures of carbamoyl radicals [54,55].

Figure 3

(a) DFT computed alpha SOMO of Ph(Me)NC^•(O) radical; (b) DFT computed spin density distribution of Ph(Me)NC^•(O) radical.

Scheme 8

Kinetic data for ring closures of carbamoyl and model radicals at 300 K in solution. Rate constants k/s⁻¹ [54,73,74,75,76].

Scheme 9

Reactions of iminyl radicals derived from oxime carbonates [33,78].

Figure 4

DFT computed reaction coordinates for spiro (red) and endo (blue) ring closure of benzofuro-iminyl radical 55a.

Scheme 10

Reaction channels and rate constants for alkoxycarbonyloxyl radicals [23,81,83].

Figure 5

(a) DFT computed SOMO for diethylaminyl radicals; (b) Spin density distribution.

Scheme 11

Photochemical reactions of oxime carbamates [95].

Scheme 12

Radical addition to oxime ethers and radical induced dissociations [99].

Scheme 13

MW assisted preparations of dihydropyrroles, aza-arenes and quinazolines from O-phenyl oxime ethers [30,103].

Scheme 14

Cyclisations of O-phenyl and O-methyl oxime ethers [104,105].

Scheme 15

Photoredox catalyzed reactions of O-aryl oxime ethers [107,108].