Alkenes catalytic nitrile oxide reactions

Accordingly, cyclic nitronates can be a useful synthetic equivalent of functionalized nitrile oxides, while reaction examples are quite limited. Thus, 2-isoxazoline N-oxide and 5,6-dihydro-4H-l,2-oxazine N-oxide, as five- and six-membered cyclic nitronates, were generated in-situ by dehydroiodination of 3-iodo-l-nitropropane and 4-iodo-l-nitrobutane with triethylamine and trapped with monosubstituted alkenes to give 5-substituted 3-(2-hydroxyethyl)isoxazolines and 2-phenylperhydro-l,2-oxazino[2,3-fe]isoxazole, respectively (Scheme 7.26) [72b]. Upon treatment with a catalytic amount of trifluoroacetic acid, the perhydro-l,2-oxazino[2,3-fe]isoxazole was quantitatively converted into the corresponding 2-isoxazoline. Since a method for catalyzed enantioselective nitrone cycloadditions was established and cyclic nitronates should behave like cyclic nitrones in reactivity, there would be a good chance to attain catalyzed enantioselective formation of 2-isoxazolines via nitronate cycloadditions. 

New isoxazoline derivatives of a-tocopherol, the main component of vitamin E, have been synthesized in a facile, two-step sequence consisting of nitration followed by 1,3-dipolar cycloaddition. 5-Nitromethyl-a-tocopheryl acetate, obtained from a-tocopheryl acetate by direct nitration in one step, act as the nitrile oxide precursor in the reaction with various alkenes. The facile conversion proceeds in the presence of equimolar amounts of PhNCO and catalytic amounts of triethylamine to give isoxazolines, 446 (489). 

Recently, the intramolecular nitrile oxide-alkene cycloaddition sequence was used to prepare spiro- w(isoxazolines), which are considered useful as chiral ligands for asymmetric synthesis (321). Reaction of the dibutenyl-dioxime (164) (derived from the diester 163) with sodium hypochlorite afforded a mixture of diastereomeric isoxazolines 165-167 in 74% combined yield (Scheme 6.80) (321). It was discovered that a catalytic amount of the Cu(II) complex 165-Cu(acac)2, where acac = acetylacetonate, significantly accelerated the reaction of diisopropylzinc... 

The most widely used, and often most convenient reagents for such one-pot reactions are sodium hypochlorite (45) or hypobromite (16). These reactions are performed in the presence of an organic base (generally triethylamine) that normally enhances the yield of cycloaddition products (45). This method was employed for many intermolecular reactions (71) and also seems especially suited for intramolecular ones (72-77) as well as for the solid-phase synthesis (78) of 2-isoxazolines. Hypohalite can also be replaced by sodium bromite in combination with a catalytic amount of tri-n-butyltin chloride (79). In a related method, O-tributylstannyl oximes were treated with fert-butyl hypochlorite to produce nitrile oxides that were trapped with alkenes or alkynes to afford the corresponding isoxazolines or isoxazoles in moderate to good yield (80). 

Besides organocatalysts, metal complexes show catalytic activities in various types of [3+2]cycloaddition. Thus Ru complex 140 performs a role in the reaction of nitrile oxides with enals, and gold(l) benzoate complex of Cy-SEGPHOS is involved in the reaction of miinchnones with alkenes. "... 

Zhdankin et al. reported the iodine(III) catalyzed oxidative cycloaddition of aldoximes 60 with alkenes and alkynes to prepare isoxazoles and isoxazolines. The active hypervalent iodine(III) species was generated in situ by the oxidation of catalytic 3,5-dimethyliodobenzene using Oxone as an inexpensive and environmentally safe terminal oxidant in aqueous 1,1,1,3,3,3-hexafluoroisopropanol (HFIP). This activated iodine(III) promoted the oxidation of the corresponding aldoximes efficiently affording nitrile oxides 61, which upon cycloaddition reaction with various alk5mes 62 and alkenes 64 resulted in isoxazoles 63 and isoxazolines 65, respectively in moderate-to-excellent yields (up to 92%). In this oxidative conversion, HFIP is believed to increase the electrophilicity of I(III) reagent (Scheme 11) [27]. 

Instead of the expected cyclopropanation products, iso-xazolines have been reported to be produced in fair yields from ethyl nitroacetate and alkenes on treatment with hydro-talcite (Mg Al = 3 1 HT calcined and rehydrated, a Brpnsted type catalyst) and catalytic iodine in refluxing toluene. Nitrile oxide seems to be ruled out as an intermediate of this reaction, as no fiiroxans have been detected [45]. 

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