Synthesis of 5-Vinyl-2-isoxazolines by Palladium-Catalyzed Intramolecular O-Allylation of Ketoximes

Abstract

An efficient method for the synthesis of 5-vinyl-2-isoxazolines by Pd-catalyzed intramolecular O-allylation of ketoximes has been developed. The reaction involves Pd(0)-catalyzed π-allyl formation via leaving group ionization or Pd­(II)-catalyzed allylic C–H activation followed by intramolecular nucleophilic oxime oxygen attack. This methodology has been elaborated to various value-added products by epoxidation, Wacker oxidation, cross-metathesis, hydroboration–oxidation, dihydroxylation, and catalytic hydrogenation.

Copper-catalyzed aerobic nitrogen-migration cyanation and oxygenation of unsaturated ketoximes via the CC bond cleavage: facile access to 4-oxobutanenitriles

“…Based on the present results and the precedent literatures, 5–8 the plausible mechanism for the aerobic nitrogen-migration cyanation and oxygenation of pent-4-en-1-one oximes was proposed (Scheme 3). Oxime 1a undergoes single electron oxidation by the active [Cu I ] species, which is generated from the oxidation of the Cu 0 species by O 2 , to form the nucleophilic iminoxyl nitrogen-centered radical A .…”

“…1,2 Among them, unsaturated ketoximes are unique owing to the presence of three reactive functional groups in them, namely an oximyl oxygen atom, an oximyl nitrogen atom and an alkene, and have been well used in alkene difunctionalization or hydrohetero-functionalization involving an intramolecular cyclization process for selectively constructing O- and N-heterocyclic frameworks. 2–5 Classical approaches are the direct activation of the CC bond moiety to generate the external functional group addition intermediate and subsequent intramolecular cyclization using the electrophilic addition, 3 oxidative organocatalysis 4 or transition-metal oxidative catalysis 5 (Scheme 1a). These methods focus on initiating the reaction from the unsaturated bond side and limit the range of the incorporated external functional groups because their success depends on the rational adjustment of the reactivity of the external attack reagents versus the nucleophilicity of the intrinsic oximyl group.…”

“…While the electrophilic alkene difunctionalization reactions selectively furnish O- and N-heterocycles relying on the position of the tethered olefins, 3 the catalytic approaches are exclusively restricted from terminating the reaction by oxygenation with the inherent O-nucleophilic groups for the synthesis of O-heterocycles. 4,5 Alternatively, Han et al have reported a radical strategy that consisted of initiating the difunctioanlization of alkenes of unsaturated ketoximes from the oxime side via radical addition across the CC bond-enabled intramolecular 5-exo-trig cyclization, followed by radical coupling with TEMPO or DEAD (Scheme 1b). 6 a This method allows the dioxygenation, oxyamination and diamination of the alkenes, respectively, to selectively assemble the five-membered N- and O-heterocycles by simply devising the position of the tethered olefins.…”

Palladium-Catalyzed Oxidant Dependent Switchable Aza-Wacker Cyclization and Oxidative Dimerization of Benzimidates

“…In continuation to our efforts in π-allylpalladium chemistry and our recent contribution (Scheme D), we visualized the synthesis of 2-aryl-4-vinyl-4,5-dihydrooxazole 12 from O -homoallyl benzimidates 6a (Scheme E) through allylic C–H activation leading to π-allylpalladium formation, which would be attacked intramolecularly by pendent imino group similar to formation of 11 . However, a careful analysis of the reaction indicated the formation of not vinyl oxazole 12 but a 1,3-oxazine 13a obtained in 53% yield (Scheme E).…”

Efficient enantioselective synthesis of pyrazolines and isoxazolines enabled by an iridium-catalyzed intramolecular allylic substitution reaction

“…15 The metal-catalyzed intramolecular O -allylation reaction has been applied for the synthesis of cyclic oxime ethers. For example, Fernandes 16 et al developed the synthesis of racemic vinyl substituted isoxazolines by Pd-catalyzed intramolecular O -allylation of ketoximes. Recently, Carreira's 17 group developed iridium-catalyzed intramolecular O -allylation of oximes to form a few chiral cyclic oxime ethers in moderate yield and excellent enantioselectivity.…”