Nitrile oxides nitromethyl compounds

Among heteroaromatic compounds able to react with nitrile oxides as dipo-larophiles, furan, probably, is the best known. Recently, a novel nitrile oxide was generated from a sulfoximine and converted in situ to a cycloadduct with furan (Scheme 1.25) (287). The starting racemic N-methyl-S-nitromethyl-S-phenylsul-foximine 124 was prepared in 87% yield via nitration of N,S-dimethyl-S-phenyl-sulfoximine. Reaction of 124 with p-chlorophenyl isocyanate and a catalytic quantity of triethylamine, in the presence of furan, afforded dihydrofuroisoxazole 125, the product of nitrile oxide cycloaddition, in 42% yield (65 35 diastereomer ratio). The reaction of 125 with phenyllithium and methyllithium afforded compounds 126, which are products formed by replacement of the sulfoximine group by Ph and Me, respectively. 

The principal sources of nitrile oxides are oximes, hydroximoyl halides, and nitromethyl compounds. They have, however, also been identified as intermediates in various other reactions, and these could be used for the preparation of furoxans. In the following paragraphs the most preparatively useful methods are identified. 

Protected ribofuranosyl 1,3-dipoles have been used as intermediates in some novel C-nucleoside syntheses. Thus, isoxazoline 153 was obtained by cycloaddition of the nitrile oxide, generated in situ from the nitromethyl compound and HiNCO, with yl aoylaie cleavage of the N-0 bond with Mo(CO)6 and subsequent reaction with hydrazine led to the pyridazinone C-... 

Nitromethyl ketones react with p-toluenesulfonic acid (PTSA) in refluxing toluene to give the corresponding furo-xans in 97% yield [20]. When refluxed several hours in xylene or mesitylene in the presence of dipolarophiles and catalytic PTSA, not only activated nitro compounds but also phenylnitromethane and 1-nitropropane afforded the expected isoxazole derivatives, as a result of nitrile oxide cycloadditions [21]. Microwave irradiation in the presence of catalytic PTSA has been successfully applied to condensations between methyl nitroacetate and dipolarophiles [22]. Nitroacetic esters have been converted into the corresponding furoxans with cold sulfuric acid [23], while phenylnitromethane and phenylacetylene in ethereal boron trifluoride etherate are reported to give 3,5-diphenylisoxazole [24]. 

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