Isoxazolidines elimination reactions

Nitronates derived from primary nitroalkanes can be regarded as a synthetic equivalent of nitrile oxides since the elimination of an alcohol molecule from nitronates adds one higher oxidation level leading to nitrile oxides. This direct / -elimination of nitronates is known to be facilitated in the presence of a Lewis acid or a base catalyst [66, 72, 73]. On the other hand, cycloaddition reactions of nitronates to alkene dipolarophiles produce N-alkoxy-substituted isoxazolidines as cycloadducts. Under acid-catalyzed conditions, these isoxazolidines can be transformed into 2-isoxazolines through a ready / -elimination, and 2-isoxazolines correspond to the cycloadducts of nitrile oxide cycloadditions to alkenes [74]. 

Nitroisoxazolines were prepared from ALalkoxy-3,3-dinitroisoxazolidines by thermally induced P-elimination. For example, isoxazolidines 42 synthesized by a three-component reaction of tetranitromethane with two equivalents of alkenes 41, were converted into isoxazolines 43 by heating in boiling chlorobenzene <06S706>. 

At the same time, the reactions of isoxazolidines (239) with soft acids and retain LA (157, 341, 398, 399) resemble an analogous process considered above for iV-siloxynitroso acetals, which also affords isoxazolines (240). Methanol can be eliminated from nitroso acetals (239) also upon heating (341). 

If X = AcO, intermediate SENA can be trapped by methyl acrylate in the [3+ 2]-cycloaddition reaction (isoxazolidine (416)). If X=C1, attempts to trap silyl nitronate failed however, nitroethylene was detected in a Diels-Alder reaction. By contrast, SENAs, in which X=OSiMe3 or NHPh, are quite stable. Therefore, the substituents X can be arranged in the following series of increasing elimination rates of SiX Cl > AcO > > PhNH. 

The elimination proceeds rapidly at room temperature with a catalytic amount of acid or fluoride, however, it has also been observed to occur upon distillation of the isoxazolidine (16,18). Because of the facile elimination, several procedures have been developed in which the reaction is quenched with an acidic agents, and the isoxazoline is isolated directly (108). Isoxazolines are useful in the preparation of p-hydroxy ketones and amino alcohols (138). 

The reactions of nitrones with 165 have been described (277-279). In the approach described by Koskinen and co-workers (279), the bulky nitrone 166 was used in a reaction with 165 to give a 20 1 mixture of 167 and an unidentified diastereomer (Note Opposite enantiomers are shown here). Reactions of less bulky nitrones gave lower selectivities (277,278). Kim et al. (280,281) described reactions of 165 with silyl nitronates (Scheme 12.52). The configuration of the direct isoxazolidine products was not determined. Instead, diastereoselectivities of 66-88% de of 169 were found after elimination of the silyloxy group. The reaction of various nitrile oxides proceeded to give the same isoxazoline products 169 as obtained for nitronates (Scheme 12.52). For the reactions of 165 with various alkyl and aryl nitrile oxides 170, the products 169 were obtained with diastereoselectivities of 62-90% de (282-286). In a theoretical study, it was proposed that the... 

The isoxazolidines (47) and (48) were obtained by cyclization of the corresponding ketone-derived exocyclic nitrones (Scheme 11).22 Such reactions have been used for natural product sysnthesis, as in the conversion of isoxazolidine (49) to ( )-hirsutene. Methylation and catalytic hydrogenolysis provided a y-dimethylamino alcohol, which underwent Cope elimination to provide an alkenyl alcohol in a key step. A related synthesis of ( )-7,12-sechoishwaran-12-ol is also reported. 

When isoxazolidines are treated with an acid, N—O cleavage and further reactions take place. With Af-hydroxy- or Af-alkoxy-isoxazolidines, sometimes water or alcohol is eliminated to give 2-isox azolines. 

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