Isoxazolines alkyl nitronates

The addition of nitronates to alkenes opens up a route to isoxazolidines, useful precursors for the synthesis of 2-isoxazolines. Tandem [4+2]/[3+2] cycloaddition reactions of nitroalkanes involving cyclic alkyl nitronates have been reported by Denmark et al. ... 

Alkyl and silyl nitronates are, in principle, /V-alkoxy and /V-silyloxynitrones, and they can react with alkenes in 1,3-dipolar cycloadditions to form /V-alkoxy- or /V-silyloxyisoxaz.olidine (see Scheme 8.25). The alkoxy and silyloxy groups can be eliminated from the adduct on heating or by acid treatment to form 2-isoxazolines. It should be noticed that isoxazolines are also obtained by the reaction of nitrile oxides with alkenes thus, nitronates can be considered as synthetic equivalents of nitrile oxides. Since the pioneering work by Torssell et al. on the development of silyl nitronates, this type of reaction has become a useful synthetic tool. Recent development for generation of cyclic nitronates by hetero Diels-Alder reactions of nitroalkenes is discussed in Section 8.3. 

Complexes of nickel(II) or magnesium(II) with the chiral ligand DBFOX (Scheme 8) catalyze the DCR of nitrones with a-alkyl- and arylacroleins rendering preferentially the 5-carbaldehyde cycloadducts. However, the reactions with a-bromoacrolein catalyzed by the zinc(II) complex of the same ligand afford isoxazoline -carbaldehydes. The corresponding cobalt(II) complex is also active for the cycloaddition between cyclopenten-l-carbaldehyde and diphenylnitrone. 

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... 

Nitronates, particularly silyl nitronates, are often superior to nitrile oxides in their 13DC with olefins in terms of their ease of generation from nitroalkanes, stability, and the observed selectivity during cycloaddition. Cycloaddition of alkyl or silyl nitronates with olefins generates N-alkoxy- or N-silyloxy-substituted isoxazolidines which then undergo spontaneous or acid catalyzed elimination of alcohol (or silanol) to produce isoxazolines (see Scheme 1, Sect. 2). 

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