Nitronic esters derived from primary nitro ketones, ethyl nitroacetate, and (phenylsulfonyl)nitromethane react with dipolarophiles in the presence of nonaqueous protic and Lewis acids to give nitrile oxide cycloadducts. a-Nitro ketones, ethyl nitroacetate, and (phenylsulfonyl)nitromethane give nitrile oxide cycloadducts in the presence of p-toluenesulfonic acid, although conditions are necessarily more vigorous. The anions of phenylnitromethane and 1-nitropropane react similarly under mild conditions, the latter in poor yield. The methyl nitronic ester of (phenylsulfonyl)nitromethane undergoes direct cycloaddition to 1-hexene in neutral media to give diastereomeric isoxazolidines. 3-(a-Hydroxyalkyl)isoxazolines are readily prepared by reduction of 3-carbethoxyisoxazolines with sodium borohydride and by carbonyl addition to 3-acylisoxazolines with alkyllithium reagents. 3-Alkenylisoxazolines, which can be prepared from either 3-(hydroxyalkyl)isoxazolines or 3-sulfonylisoxazolines, undergo reversible [4 + 2]-cycloaddition with tetracyanoethylene.The diverse reactions of nitro compounds, nitronate salts, and nitronic esters with aqueous acid have been under study for over a century.1 Aldehydes and ketones are most commonly obtained (the Nef reaction). Under strongly acidic conditions, hydroxamic acids are formed instead; these may further hydrolyze to carboxylic acids and hydroxylamine (the Meyer reaction). Hydroxamic acid formation has been shown to proceed through hydrolysis of a nitrile oxide intermediate.2 Surprisingly little synthetic use has been made of this demonstration. Furoxans (1,2,5-oxadiazole 2-oxides) have been prepared from several nitro compounds under strongly acidic conditions,3 but extensive studies of nitrile oxide cycloadditions to added dipolarophiles are conspicuously lacking.
X-ray Analysis of 2a. Single crystals of 2a were tetrahedral, space group P43 (for the configuration shown in Figure 1) or P4lt with a -12.896 (1) Á, c = 13.773 (3) A, and d^= 1.300 g cm"1 23 for Z = 4 (CggHgjjOg, mol wt 448.47). The intensity data were measured on a Hilger-Watts diffractometer (Ni-filtered Cu Ka radiation, 0-20 scans, pulse-height discrimination). A crystal measuring approximately 0.30 X 0.6 X 0.6 mm was used for data collection. A total of 1616 reflections was measured for 0 < 57°, of which 1570 were considered to be observed [/ > 2.5»(/)]. The structure was solved by a multiple solution procedure13 and was refined by full-matrix least-squares. In the final refinement (13)
Racemic N-methyl-S-(nitromethyl)-S-phenylsulfoximine (2) was prepared in 87% yield via alkaline nitration of N,S-dimethyl-S-phenylsulfoximine. Optically active N-methyl-S-(nitromethyl)-S-phenylsulfoximine (both enantiomers) was prepared in similar fashion. Reaction of racemic 2 with p-chlorophenyl isocyanate and a catalytic quantity of triethylamine in the presence of furan afforded dihydrofuroisoxazole 5, the product of nitrile oxide cycloaddition, in 42% yield (65:35 diastereomer ratio). Reaction of the dihydrofuroisoxazole 5 with phenyllithium and methyllithium afforded replacement of the sulfoximine group by phenyl and methyl, respectively. Reaction of racemic 2 with aromatic isocyanates and potassium carbonate afforded C-acylation products in 70-78% yield which existed as the ylide tautomers 9a,b. Methylation of racemic 2 afforded the C-alkylate N-methyl-S-(1-nitroethyl)-S-phenylsulfoximine (13), existing as the neutral tautomer.
3-(Phenylsulfonyl)isoxazolines, readily obtained from alkenes by cycloaddition with benzenesulfonylcarbonitrile oxide, undergo a variety of substitution reactions. Alkyl, aryl, and acetylenic lithium reagents, cyanide, lithium or sodium alkoxides, and sodium borohydride are all useful nucleophiles. Tandem alkylations are possible with alkyllithium reagents when excess base and alkyl iodide are used. Excess base can also be used to cleave the isoxazoline ring of the initial substitution products. 3-(2-Propenyloxy)isoxazolines will undergo an aza-Claisen rearrangement on heating.
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